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Background: The proposed research study introduces independent concentration extraction (ICE) as a novel UV-Vis spectrophotometric approach. The approach can be used for extracting the concentration of two analytes with severely overlapped spectra from their binary mixtures. ICE is based on spectral extraction platform involving simple smart successive methods that can directly extract the original zero order spectra of the analytes at their characteristic (λ max ). Chlorpheniramine maleate (CPM) and Levocloperastine fendizoate (LCF) are two commonly co-formulated drugs in cough preparations. The combined mixture was used to confirm the validity of the developed ICE tool. Another less green HPTLC was developed for the first time to separate both drugs and help also in confirming the proposed tool., Methods: For the simultaneous determination of CPM and LCF, two ecologically friendly techniques were employed. The first approach encompasses the use of the ICE spectrophotometric method that could be successively applied for extracting the concentration of two analytes with severely overlapped unresolved spectra in their binary mixtures. Other complementary methods aiming at original spectral extraction; including spectrum subtraction (SS) and unity subtraction (US) were also successfully employed to resolve the zero order spectra of the combined drugs with all their characteristic features and peaks. The second technique used, a high-performance TLC-densitometric one, was performed on silica plates with silica plates F254 and a mobile phase with a ratio of 3:3:3:1 by volume of toluene, ethanol, acetone, and ammonia as a developing system at 230 nm., Results: The presented extraction approach was executed without any optimization steps or sample pretreatment for the simultaneous determination of CPM and LCF. The method was found to be valid for their determination within concentration range of 3.0-30.0 μg mL -1 for both drugs. For HPTLC method, the resulting R f values of CPM and LCF were 0.37 and 0.78, within concentration ranges of 0.3-4.0 μg/spot and 0.8-10.0 μg/spot, respectively. Greenness assessment of both developed methodologies showed that the HPTLC method is less green than the spectrophotometric method, yet with comparable sustainability when it comes to the used technique., Conclusion: The procedures were found to be selective, accurate, and precise for analysis of the studied binary mixture. Furthermore, the environmental impact of the introduced methods was assessed using novel greenness metrics, namely AGREE and Green Analytical Procedure Index (GAPI) to prove their ecological safety. In addition, white analytical chemistry (WAC) evaluation metric was employed to ensure the synergy and coherence of analytical, practical, and ecological attributes., (© 2024. The Author(s).)

Chlorpheniramine Maleate (CPM), also known as chlorphenamine, is a potent alkylamine first-generation H1 antihistamine that has been used since the 1950s. CPM is a widely popular drug commonly used to treat allergic conditions, given its antihistamine properties. Although mainly used in over-the-counter treatment for cough and colds, various studies discuss a wide range of CPM's clinical uses, such as treating asthma, plasma cell gingivitis, chronic urticaria, and depression, among others. This antihistamine is usually taken orally; however, intravenous, intramuscular, and subcutaneous routes have been documented. Intranasal routes of this drug have recently been explored, especially due to its antiviral properties against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accordingly, given CPM's extensive medical and safety profile, the present review explores this versatile drug's current and potential clinical applications. Although it is widely used mainly for treating common colds and aforementioned allergic conditions, CPM can be used for other clinical indications. The repurposing of CPM for other clinical indications, such as COVID-19, needs to be further explored through more extensive studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The Keteling capsule (KC) is a traditional Chinese medicine (TCM) made from the dried extract of Ficus microphylla and an appropriate amount of chlorpheniramine maleate. It is widely used to treat cough and relieve asthma. Despite its extensive usage, a rapid and comprehensive quality evaluation strategy for KC remains a challenge. This study introduces an electrochemical fingerprint analysis technique, in addition to the commonly employed HPLC fingerprints, for efficient and convenient quality evaluation. Moreover, a cost-effective, rapid, and accurate multi-component quantification technique known as the "Multi-markers assay by the monolinear method (MAML)" and the "FT-IR quantitative model" were explored. The HPLC fingerprints were evaluated using a systematically quantified fingerprint method, while the electrochemical fingerprints, based on the Belousov-Zhabotinsky oscillation reaction principle, were effectively analyzed and characterized using oxidation induction times and oscillation lifetimes. Multi-component quantitative analysis was carried out through the MAML and FT-IR quantitative models. The HPLC fingerprint successfully classified the 22 samples into eight grades with excellent discrimination. Active ingredient content analysis was achieved using reliable parameters obtained from electrochemical fingerprinting. The no significant difference in the quantitative results proves the accuracy of the MAML method. Additionally, successful FT-IR quantitative prediction models were developed for chlorogenic acid, isovitexin, and chlorpheniramine maleate. This study offers a dependable and effective approach for enhancing the quality control of KC, and it can provide new insights for improving the quality analysis methods in the field of TCM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chlorpheniramine (CPM) and Ciprofloxacin (CIP) adsorption onto a granular (GAC) and pelletized activated carbon (PAC) analyzing the physicochemical mechanisms involved using the carbon's characterization were studied. Adsorption isotherm studies were performed at temperatures of 25 °C at pH values of 4, 7 and 9 and at 45 °C at a pH of 7. The characterization demonstrated that GAC has a predominantly acid character due to its predominantly negative surface charge and acidic site concentration alongside the characteristic bands detected in the X-ray Photoemission Spectroscopy (XPS) study. On the other hand, PAC presented a mostly basic character due to its positive surface charge and basic site concentrations. The adsorption isotherm studies demonstrated that the Freundlich isotherm better described the equilibrium data with an average deviation percentage of 7.45 and 6.74 for GAC and PAC. The temperature and desorption studies demonstrated that the adsorption process occurs through a chemisorption mechanism, and the pH study alongside the GAC and PAC characterization demonstrated that the mechanisms involved are a combination of electrostatic interactions and pi-pi interactions between the CPM and CIP molecules and the carbon's surface. These results demonstrate that the adsorption process of these pharmaceutical compounds is done through a combination of physical and chemical interactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Chlorphenamine (CPA) adsorption onto three activated carbons (ACs), namely, Megapol M (MM), Micro 10 (M10), and GAMA B (GB), was studied in this work. The textural properties, concentrations of active sites, surface charge and point of zero charge of the ACs were assessed. The surface areas (S BET ) of MM, GB and M10 were 1107, 812 and 766 m 2 /g, respectively. The MM surface had an acidic character, while the surfaces of M10 and GB were basic. The adsorption capacity of MM, M10, and GB towards CPA was studied at pH 7 and 11, and the adsorption capacity decreased in the order MM > M10 ≈ GB, which was ascribed to the magnitude of S BET and the concentration of acidic sites. The solution pH significantly increased the adsorption capacity of MM towards CPA by raising the solution pH from 5 to 9, and this behavior was attributed to the electrostatic attraction between the negatively charged surface of MM and the cationic species of CPA. The maximum uptake of CPA adsorbed on MM was 574.6 mg/g at pH = 11 and T = 25 °C. The adsorption capacity of MM was slightly raised by incrementing the temperature. Lastly, the zeta potential measurements of pristine MM and MM saturated with CPA confirmed that the electrostatic attraction predominated in the pH range of 5-9, and the π-π stacking interactions were the principal mechanism of CPA adsorption on MM at pH 11., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Loratadine (LRD), a non-sedating and slow-acting antihistamine, is often given in combination with short-onset chlorpheniramine maleate (CPM) to increase efficacy. However, LRD has poor water solubility resulting in low bioavailability. The aim of this study was to improve LRD solubility by preparing co-amorphous LRD-CPM. However, the obtained co-amorphous LRD-CPM recrystallized rapidly, and the solubility of LRD returned to a poor state again. Therefore, co-amorphous LRD-CPM solid dispersions using polyvinylpyrrolidone (PVP) as a carrier were prepared. The obtained solid dispersions were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). The solubility, dissolution, and mechanism of drug release from the LRD-CPM/PVP co-amorphous solid dispersions were studied and compared with those of intact LRD, LRD/PVP solid dispersions, and co-amorphous LRD-CPM mixtures. The results from XRPD and DSC confirmed the amorphous form of LRD in the co-amorphous solid dispersions. The FTIR results indicated that there was no intermolecular interaction between LRD, CPM, and PVP. In conclusion, the obtained LRD-CPM/PVP co-amorphous solid dispersions can successfully increase the water solubility and dissolution of LRD and extend the amorphous state of LRD without recrystallization.

The first-generation antihistamine chlorpheniramine (CPA) is believed to have both anxiolytic and antidepressant properties. The current study sought to assess the mechanisms behind the antidepressant and anxiolytic effects of CPA therapy concerning oxidative stress, inflammation, and nuclear factor p45 for erythroid 2-Brain-derived neurotrophic factor (Nrf2-BDNF) signaling pathway in forced swimming-induced depressive-like behavior and anxiety. Eighteen male Wistar rats (180-200 gm) rats were separated into three groups (n = 6): a stressed group (acute stress) that underwent the forced swimming test (FST) and a stressed group that received pretreatment with CPA (10 mg/kg body weight) for 3 weeks (CPA + acute stress). Animals were subsequently put through the following behavioral tests after undergoing a forced swim test (FST) for 5 min: an immobility test, open field test, and elevated plus maze test. Serum cortisol levels were measured when the rats were euthanized at the end of the experiments. Brain neurotransmitters (cortisol, serotonin, and noradrenaline), oxidative stress (SOD and MDA), inflammatory (IL-6 and IL-1) biomarkers, and the Nrf2-BDNF signaling pathway in the hippocampus and cerebral cortex tissues was determined. CPA prevented stress-induced increases in cortisol levels ( p < 0.0001), decreased brain neurotransmitters, and increased oxidative stress and inflammation. CPA also upregulated the Nrf2-BDNF signaling pathway. Thus, CPA mitigates depressive-like behavior and anxiety by inhibiting oxidative stress and inflammation and upregulating the Nrf2-BDNF signaling pathway in the brain tissues.

In Asian developing countries, undeveloped and ineffective sewer systems are causing surface water pollution by a lot of contaminants, especially pharmaceuticals and personal care products (PPCPs). Therefore, the risks for freshwater fauna need to be assessed. The present study aimed at: i) elucidating the contamination status; ii) evaluating the bioaccumulation; and iii) assessing the potential risks of PPCP residues in surface water and freshwater fish from three Asian countries. We measured 43 PPCPs in the plasma of several fish species as well as ambient water samples collected from India (Chennai and Bengaluru), Indonesia (Jakarta and Tangerang), and Vietnam (Hanoi and Hoa Binh). In addition, the validity of the existing fish blood-water partitioning model based solely on the lipophilicity of chemicals is assessed for ionizable and readily metabolizable PPCPs. When comparing bioaccumulation factors calculated from the PPCP concentrations measured in the fish and water (BAF measured ) with bioconcentration factors predicted from their pH-dependent octanol-water partition coefficient (BCF predicted ), close values (within an order of magnitude) were observed for 58-91 % of the detected compounds. Nevertheless, up to 110 times higher plasma BAF measured than the BCF predicted were found for the antihistamine chlorpheniramine in tilapia but not in other fish species. The plasma BAF measured values of the compound were significantly different in the three fish species (tilapia > carp > catfish), possibly due to species-specific differences in toxicokinetics (e.g., plasma protein binding and hepatic metabolism). Results of potential risk evaluation based on the PPCP concentrations measured in the fish plasma suggested that chlorpheniramine, triclosan, haloperidol, triclocarban, diclofenac, and diphenhydramine can pose potential adverse effects on wild fish. Results of potential risk evaluation based on the PPCP concentrations measured in the surface water indicated high ecological risks of carbamazepine, sulfamethoxazole, erythromycin, and triclosan on Asian freshwater ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The purpose of the study is to develop and assess mucoadhesive in situ nasal gel formulations of loratadine and chlorpheniramine maleate to advance the bioavailability of the drug as compared to its conventional dosage forms. The influence of various permeation enhancers, such as EDTA (0.2% w / v ), sodium taurocholate (0.5% w / v ), oleic acid (5% w / v ), and Pluronic F 127 (10% w / v ), on the nasal absorption of loratadine and chlorpheniramine from in situ nasal gels containing different polymeric combinations, such as hydroxypropyl methylcellulose, Carbopol 934, sodium carboxymethylcellulose, and chitosan, is studied. Among these permeation enhancers, sodium taurocholate, Pluronic F127 and oleic acid produced a noticeable increase in the loratadine in situ nasal gel flux compared with in situ nasal gels without permeation enhancer. However, EDTA increased the flux slightly, and in most cases, the increase was insignificant. However, in the case of chlorpheniramine maleate in situ nasal gels, the permeation enhancer oleic acid only showed a noticeable increase in flux. Sodium taurocholate and oleic acid seems to be a better and efficient enhancer, enhancing the flux > 5-fold compared with in situ nasal gels without permeation enhancer in loratadine in situ nasal gels. Pluronic F127 also showed a better permeation, increasing the effect by >2-fold in loratadine in situ nasal gels. In chlorpheniramine maleate in situ nasal gels with EDTA, sodium taurocholate and Pluronic F127 were equally effective, enhancing chlorpheniramine maleate permeation. Oleic acid has a better effect as permeation enhancer in chlorpheniramine maleate in situ nasal gels and showed a maximum permeation enhancement of >2-fold.

Objective: To describe the price and affordability of key essential medicines for children in the private sector in Sri Lanka in 2017/2018, and compare the findings with 2009 data., Design: National cross-sectional descriptive survey using the WHO/Health Action International medicine price methodology., Setting and Participants: Data were collected from a representative sample of 54 private sector pharmacies selected from all 9 provinces in Sri Lanka using a multistage clustered approach., Main Outcomes: Median price ratio (MPR) and affordability of originator brand (OB) and lowest priced generics (LPG) of 25 key essential medicines for children., Results: The median MPR was 2.69 for OBs and 1.45 for LPGs compared with 3.7 and 1.35 in 2009. MPR of OB of all but one (chlorphenamine syrup) were higher than that of the LPG. MPR-OB>5 was observed for ceftriaxone injection, amoxicillin capsule, mebendazole chewable tablet and metronidazole tablet. This was documented in 2009 as well except for amoxicillin capsule. Prices of LPGs of seven medicines (amoxicillin capsule, amoxicillin suspension, clotrimazole cream, mebendazole chewable tablet, metronidazole tablet) were estimated as excessive (MPR ≥2.5) compared with chlorphenamine syrup, clotrimazole topical cream, ibuprofen syrup and paracetamol syrup in 2009. Compared with 2009, MPRs of OBs of 8 medicines and LPGs of 12 medicines were higher in 2017/2018. Compared with 2009, no change in affordability was noted except for asthma, which has been assessed as affordable in 2017/2018. Standard drug therapy for mild lower respiratory tract infections and acute gastroenteritis remained affordable, and treating epilepsy with carbamazepine syrup remained unaffordable., Conclusion: Economic access to key essential medicines for children has not improved in Sri Lanka in the 8 years' time since the initial survey in 2009., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Protamine administration post-cardiopulmonary bypass (CPB) can potentially cause hemodynamic instability. Histamine released from mast cells is believed to be responsible for hypotension after protamine administration. The aim of this study was to examine the effects of pretreatment with H1 and H2 antihistamines on changes in systemic arterial pressure following protamine administration., Methods: This study was a randomized, triple-blinded, placebo-controlled study, conducted at a university hospital. Forty adult patients undergoing elective coronary artery bypass grafting (CABG) or single valve surgery were included. The patients were randomly allocated (20 patients in each group) to receive a single dose of combined chlorpheniramine 10 mg and ranitidine 50 mg or normal saline intravenously immediately after separation from CPB prior to protamine administration. Trajectory changes in systolic blood pressure (SBP), mean arterial pressure (MAP), and vasoactive-inotropic score (VIS) from baseline until 35 minutes following protamine administration (24-time points) were compared between the two groups. Serial serum tryptase levels were also obtained at baseline, 30 and 60 minutes after protamine was given., Results: Forty patients were included in the analysis. Demographic and baseline blood pressure were similar between the two groups. At 30 minutes after protamine administration, there were no significant differences in both crude SBP [mean difference: -7.1 mmHg, 95% confidence interval (CI), -1.1 to 15.3 mmHg, P=0.09] and SBP after adjustment for the European System for Cardiac Operative Risk Evaluation (EuroSCORE II), CPB time, and VIS (mean difference: -3.9 mmHg, 95% CI, -11.9 to 4.0 mmHg, P=0.33). There were also no significant differences in crude MAP (mean difference: -2.1 mmHg, 95% CI, -6.9 to 2.7 mmHg, P=0.39) and adjusted MAP (mean difference: -0.7 mmHg, -5.9 to 4.4 mmHg, P=0.78) between the two groups. None of the patients in both groups had a significant increase in serum tryptase from baseline. No differences in median serum tryptase levels at baseline, 30 and 60 minutes were demonstrated between the two groups., Conclusions: Pretreatment with H1 and H2 antihistamines does not attenuate blood pressure responses to protamine administration in patients after CPB. Mechanisms other than histamine release from mast cells might be responsible for protamine-induced cardiovascular changes., Trial Registration: ClinicalTrials.gov NCT03583567.

In many parts of the world, water resources are scarce or even extremely scarce, and the reuse of water resources has become mainstream in today's world. Many regions use treated wastewater for agricultural irrigation, aquaculture, and other activities. However, in recent years, wastewater has been found to contain large amounts of pharmaceuticals and personal care products (PPCPs). Therefore, there is a potential risk of PPCPs being transported in the environment and affecting human health. In this study, we compared the uptake, transport, and accumulation of 27 PPCPs in three types of sprouts (radish, buckwheat, and okra).The bioaccumulation of amantadine, diphenhydramine, chlorpheniramine maleate, sibutramine, hemosibutramine, chlorosibutramine, N-monomethyl sibutramine, N, N-desmethyl sibutramine, and carbamazepine was found to be significantly higher in plants grown for 12 days in media containing 0.5, 5.0, and 50.0 ng/mL PPCPs. With increasing concentration of PPCPs in the culture solution, the amount of PPCPs absorbed by plants and the degree of accumulation also showed an increasing trend. At the same time, it was demonstrated that there was an obvious uptake transfer phenomenon of PPCPs by plants, and the trend of uptake transfer became more and more obvious as the concentration of external environmental pollutants increased. In addition, amantadine, chlorpheniramine maleate, carbamazepine, N, N-desmethyl sibutramine, hemosibutramine, and chlorosibutramine showed more active translocation in some plants (TF > 1.0).

A general and mild strategy involving three-component carboarylation of unactivated alkenes with protic C(sp 3 )-H feedstocks via photoredox catalysis was reported. This catalytic system is compatible with a broad range of unactivated alkenes, cyano-substituted arenes, and diverse protic C(sp 3 )-H feedstocks. The synthetic value of this protocol was demonstrated by the late-stage functionalization of complex molecules and the synthesis of the antiallergies including pheniramine, chlorpheniramine, and brompheniramine.

Background: An optimal strategy for choosing safe alternative low osmolar contrast media (LOCM) has not yet been established in patients with a history of LOCM-induced anaphylaxis., Objectives: To validate the practical pathway in patients with anaphylaxis to LOCMs and to compare 2 different doses of challenge testing with skin test-negative LOCM., Methods: A retrospective cohort study was performed in patients with LOCM-induced anaphylaxis. Patients were challenged with intravenous LOCMs showing negativity in the skin test according to 2 different protocols: low-dose and high-dose (maximum dose 10 and 30 mL, respectively). Challenge-negative LOCMs were selected for use during computed tomography scans, and patients received intravenous pretreatment with 4 mg chlorpheniramine and 40 mg methylprednisolone., Results: Of the 110 challenge tests, there were 4 (3.6%) positive challenges. Among 106 enhanced computed tomography scans performed using challenge-negative LOCMs, breakthrough reactions occurred in 8 (7.6%). Breakthrough reaction rates were not statistically different between the 2 protocols (8.9% and 6.0% in the low-dose challenge and the high-dose challenge, respectively). Compared with the low-dose protocol, the number needed to test of the high-dose challenge test decreased 2.5-fold. Moreover, none of the patients in the high-dose challenge group incurred severe reactions during computed tomography scans with challenge-negative LOCM, whereas 80% of reactions were severe in the low-dose challenge group., Conclusions: We validated a pathway consisting of a battery of skin testing to LOCMs and challenge with skin test-negative LOCM in patients with LOCM-induced anaphylaxis., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Context: Antihistamines (AHs) are the most widely long-term therapeutic option to manage allergic diseases. This research aimed to study the effects of long-term administration of AHs: on cognitive (memory, mood, attention, sleep and executive function) and psychomotor performance., Materials and Methods: This prospective, observational study for a total duration of 30 months was carried out at the Dermatology OPD in adult patients with dermatological condition who were newly prescribed either chlorpheniramine (4 mg, BD), levocetirizine (10 mg, OD), fexofenadine (180 mg, OD) or bepotastine (10 mg, BD) for at least 28 days as per inclusion and exclusion criteria after taking written informed consent. A detailed history of the patients, memory (using PGI memory scale) and psychomotor functions, Brief Mood Introspection Scale and Epworth Sleepiness Scale were assessed at baseline, 1 week and 4 weeks. Data obtained were analysed using paired sample t -test and one-way ANOVA followed by post hoc analysis ( P -value <0.05 statistically significant)., Results: A total of 22 in chlorpheniramine group, 23 in levocetirizine group, 20 in fexofenadine group and 18 in bepotastine group were analysed. Chlorpheniramine and levocetirizine had deteriorating effects on cognitive and psychomotor performance, whereas fexofenadine and bepotastine showed positive effect on various cognitive and psychometric tasks. The study results showed chlorpheniramine and levocetirizine to be having sedative effects, whereas fexofenadine was nonsedating. In bepotastine group, no effect on sleep was observed. No significant difference in mood scores was observed in between chlorpheniramine, levocetirizine and fexofenadine groups. In bepotastine group, arousal calm and positive tired scores increased at 4 week as compared to baseline., Conclusion: Patients with dermatological illnesses can be prescribed fexofenedine and bepotastine, as compared to chlorpheniramine and levocetirizine, and their cognitive and psychological functions should be evaluated periodically with suitable tests., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Non-destructive analysis of chlorpheniramine maleate (CPM), pharmaceutical tablets, and granules was conducted by chemometrics-assisted attenuated total reflectance infrared spectroscopy (ATR-IR). For tablets, an optimum PLSR model with eight latent factors was obtained from area-normalized and standard normal variate (SNV) pretreated ATR-IR spectral data with correlation coefficients (R 2 ) of calibration and cross-validation of 0.9716 and 0.9602, respectively. The model capability for the 42 test set samples was proven with R 2 between the reference and model prediction values of 0.9632, and a root-mean-square error of prediction (RMSEP) of 1.7786. The successive PLSR model for granules was constructed from SNV and first derivative pretreated ATR-IR spectral data with two latent factors and correlation coefficients (R 2 ) of calibration and cross-validation of 0.9577 and 0.9450, respectively.

Background: The presence of a urinary catheter, postoperative pain, and postoperative nausea and vomiting are risk factors for emergence agitation (EA). Antimuscarinic agents are primary agents used in the prevention and treatment of urinary catheter-related bladder discomfort. Chlorpheniramine has antimuscarinic, antinociceptive, and antiemetic effects. This retrospective study investigated the role of chlorpheniramine in EA prevention following ureteroscopic stone surgery., Methods: Of 110 adult patients who underwent ureteroscopic stone surgery under general anesthesia between January and December 2019, the medical records of 93 patients were analyzed retrospectively. The patients were divided into control (n = 52) and chlorpheniramine (n = 41) groups according to the receipt of intravenous chlorpheniramine before the induction of anesthesia. The incidence and severity of EA were compared between the groups as primary and secondary endpoints, respectively. The effects of chlorpheniramine on the requirement for inhalation anesthetic (desflurane) during surgery, changes in mean blood pressure and heart rate during emergence, and adverse events were also compared., Results: The incidence (21.2% in the control group, 24.4% in the chlorpheniramine group) and severity of EA did not differ between groups. The intraoperative requirement for desflurane, changes in mean blood pressure and heart rate during emergence, and adverse events were also similar between groups., Conclusions: Chlorpheniramine was not associated with a decrease in EA incidence or severity in patients who underwent ureteroscopic stone surgery.

A chromatographic technique based on a chiral stationary phase (CSP) has been explored for enantioseparation. Herein, poly(glycidyl methacrylate) (poly(GMA)) brushes were grafted on the surface of silica gel via surface-initiated atom transfer radical polymerization (SI-ATRP), followed by the introduction of vancomycin as a chiral selector. The as-synthesized material was characterized by elemental analysis, scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) and thermogravimetric analysis (TGA), proving the formation of vancomycin-immobilized brushes. Then the resulting CSP was explored to separate 7 racemic drugs (bicalutamide, 1-benzyl-5-phenylbarbituric acid, chlorpheniramine maleate, fluoxetine hydrochloride, verapamil hydrochloride, benzoxazocine hydrochloride and isoprenaline hydrochloride) in high performance liquid chromatography (HPLC). Several factors affecting the enantioseparation performance of the vancomycin-immobilized CSP, including the triethylamine (TEA) content in the buffer, pH value, content of organic solvent in the mobile phase, flow rate and injection volume, were mainly optimized. Under the optimal conditions, baseline separation of fluoxetine hydrochloride ( R S = 1.01), chlorpheniramine maleate ( R S = 1.01), chlorpheniramine maleate ( R S = 0.77), 1-benzyl-5-phenylbarbituric acid ( R S = 0.67), isoprenaline hydrochloride ( R S = 0.73), verapamil hydrochloride ( R S = 0.91) and benzoxazocine hydrochloride ( R S = 1.03) was partly achieved. It was concluded that SI-ATRP is a robust way to fabricate vancomycin-based CSPs for enantioseparation.

Background: Toxicity from the intentional misuse of over-the-counter (OTC) combination cold products has been widely recognized. Adolescents are most frequently involved and dextromethorphan containing products are the most popular. Desired symptoms include stimulatory effects, euphoria, hallucinations, and dissociation. Potential adverse effects include tachycardia, agitation, hyperthermia, acidosis, and coma. However, mortality is rare [ 1-3]. Co-formulated ingredients such as acetaminophen, pseudoephedrine, and antihistamines may also be present and potentiate dangerous effects. We report a case of an adolescent decedent with markedly elevated postmortem chlorpheniramine (CPA) and dextromethorphan (DXM) blood concentrations and no other identifiable cause of death., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The transient histaminergic system is among the first neurotransmitter systems to appear during brain development in the rat mesencephalon/rhombencephalon. Histamine increases FOXP2-positive deep-layer neuron differentiation of cortical neural stem cells through H 1 receptor activation in vitro . The in utero or systemic administration of chlorpheniramine (H 1 receptor antagonist/inverse agonist) during deep-layer cortical neurogenesis decreases FOXP2 neurons in the developing cortex, and H 1 R- or histidine decarboxylase-knockout mice show impairment in learning and memory, wakefulness and nociception, functions modulated by the cerebral cortex. Due to the role of H 1 R in cortical neural stem cell neurogenesis, the purpose of this study was to evaluate the postnatal impact of the systemic administration of chlorpheniramine during deep-layer cortical neuron differentiation (E12-14) in the primary motor cortex (M1) of neonates (P0) and 21-day-old pups (P21). Chlorpheniramine or vehicle were systemically administered (5 mg/kg, i.p.) to pregnant Wistar rats at gestational days 12-14, and the expression and distribution of deep- (FOXP2 and TBR1) and superficial-layer (SATB2) neuronal cortical markers were analyzed in neonates from both groups. The qRT-PCR analysis revealed a reduction in the expression of Satb2 and FoxP2. However, Western blot and immunofluorescence showed increased protein levels in the chlorpheniramine-treated group. In P21 pups, the three markers showed impaired distribution and increased immunofluorescence in the experimental group. The Sholl analysis evidenced altered dendritic arborization of deep-layer neurons, with lower excitability in response to histamine, as evaluated by whole-cell patch-clamp recording, as well as diminished depolarization-evoked [ 3 H]-glutamate release from striatal slices. Overall, these results suggest long-lasting effects of blocking H 1 Rs during early neurogenesis that may impact the pathways involved in voluntary motor activity and cognition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Valle-Bautista, Márquez-Valadez, Herrera-López, Griego, Galván, Díaz, Arias-Montaño and Molina-Hernández.)

Three-dimensional (3D) electrochemiluminescence (ECL) platform with high sensitivity and good anti-fouling is highly desirable for direct and sensitive analysis of complex samples. Herein, a novel ECL-sensing platform is demonstrated based on the equipment of vertically ordered mesoporous silica-nanochannel films (VMSF) on monolithic and macroporous 3D graphene (3DG). Through electrografting of 3-aminopropyltriethoxysilane (APTES) onto 3DG as molecular glue, VMSF grown by electrochemically assisted self-assembly (EASA) method fully covers 3DG surface and displays high stability. The developed VMSF/APTES/3DG sensor exhibits highly sensitized ECL response of tris(2,2'-bipyridyl) ruthenium (Ru (bpy) 3 2+ /tri-n-propylamine (TPrA). The VMSF/APTES/3DG sensor can also sensitively detect the most effective antihistamines chlorpheniramine (with LOD of 430 nM) using ECL signal-on mode because it acts as co-reactant to promote the ECL of Ru (bpy) 3 2+ /tri-n-propylamine (TPrA). The VMSF/APTES/3DG sensor can also sensitively detect the most effective antihistamines chlorpheniramine (with LOD of 430 nM) using ECL signal-on mode because it acts as co-reactant to promote the ECL of Ru (bpy) 3 2+ . Combined with the excellent antifouling ability of VMSF, the sensor can also realize the analysis of actual environmental (lake water) and pharmaceutical (pharmacy tablet) samples. The proposed 3D ECL sensor may open new avenues to develop highly sensitive ECL-sensing platform., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gong, Tang, Luo, Zhou, Lin, Wang, Yan, Xi and Liu.)

The aim of the present work was the preparation of Li/Al nanoparticles (NPs) functionalized with graphene oxide quantum dots (GOQDs) for the controlled release of chlorpheniramine maleate (CPAM). The role of lemon and egg white extracts as oxidation agents were investigated for the morphology and particle size of the products. GOQDs were synthesized using green, environmentally friendly, and cost-effective precursors. This work demonstrates that Li/Al NPs functionalized with graphene oxide as a nanolayer structure can be used as efficient nanocarriers for loading and delivery of CPAM as water-insoluble aromatic drugs The final products were identified with X-ray diffraction, scanning electron microscopy, atomic force microscopy, ultraviolet-visible spectroscopy, dynamic light scattering, thermogravimetric analysis, and transmission electron microscopy nitrogen adsorption [i.e. Brunauer-Emmett-Teller (BET) surface area analysis] techniques. The calibration curve for Li/Al nanoparticles functionalized with GOQDs for controlled released of CPAM was calculated as y = 0.0137x + 0.0103 with R 2  = 0.9995. The data found through BET and Barrett-Joyner-Halenda analysis using the adsorption/desorption isotherm method demonstrated by total pore volumes and dead volume were calculated respectively as 0.162 nm 2 , 0.0439 cm 3 g -1 . The mean pore diameter was calculated as 20.33 nm using BET isotherm data., (© 2021 John Wiley & Sons Ltd.)

The polyelectrolyte poly(sodium 4-styrenesulfonate) undergoes aromatic-aromatic interaction with the drug chlorpheniramine, which acts as an aromatic counterion. In this work, we show that an increase in the concentration in the dilute and semidilute regimes of a complex polyelectrolyte/drug 2:1 produces the increasing confinement of the drug in hydrophobic domains, with implications in single chain thermodynamic behavior. Diafiltration analysis at polymer concentrations between 0.5 and 2.5 mM show an increase in the fraction of the aromatic counterion irreversibly bound to the polyelectrolyte, as well as a decrease in the electrostatic reversible interaction forces with the remaining fraction of drug molecules as the total concentration of the system increases. Synchrotron-SAXS results performed in the semidilute regimes show a fractal chain conformation pattern with a fractal dimension of 1.7, similar to uncharged polymers. Interestingly, static and fractal correlation lengths increase with increasing complex concentration, due to the increase in the amount of the confined drug. Nanoprecipitates are found in the range of 30-40 mM, and macroprecipitates are found at a higher system concentration. A model of molecular complexation between the two species is proposed as the total concentration increases, which involves ion pair formation and aggregation, producing increasingly confined aromatic counterions in hydrophobic domains, as well as a decreasing number of charged polymer segments at the hydrophobic/hydrophilic interphase. All of these features are of pivotal importance to the general knowledge of polyelectrolytes, with implications both in fundamental knowledge and potential technological applications considering aromatic-aromatic binding between aromatic polyelectrolytes and aromatic counterions, such as in the production of pharmaceutical formulations.

Purpose: Catheter-related bladder discomfort (CRBD) is postoperative distress caused by a urinary catheter. CRBD is related to muscarinic receptor activation. Chlorpheniramine has antimuscarinic properties. Hence, this investigation was undertaken to evaluate the efficacy of chlorpheniramine in preventing CRBD in patients undergoing transurethral resection of bladder tumor (TURBT)., Methods: Seventy-six patients scheduled for TURBT under general anesthesia were assigned into two groups. In the chlorpheniramine group (n = 38), 100 ml normal saline containing 0.1 mg/kg chlorpheniramine was infused after general anesthesia induction. In the control group (n = 38), 100 ml normal saline alone was infused. The incidence and severity of CRBD were assessed at 1, 6, and 24 h postoperatively., Results: The 1-h postoperative incidence of CRBD was lower in the chlorpheniramine group based on the unadjusted analysis [16 (42%) vs. 28 (74%), risk difference 32%, 95% confidence interval 8-51, p = 0.005]. After adjusting the size of the urinary catheter, post hoc analysis showed that the 1-h postoperative incidence of CRBD was lower in the chlorpheniramine group (p = 0.004). The CRBD severity score was lower in the chlorpheniramine group at 1 and 6 h after operation based on the unadjusted analysis (p = 0.012 and p = 0.007, respectively). After adjusting the urinary catheter size, post hoc analysis showed that 1- and 6-h CRBD severity score was lower in the chlorpheniramine group (p = 0.012 and p = 0.008, respectively). The incidence of rescue medication was lower in the chlorpheniramine group [10 (26%) vs. 20 (53%), risk difference 26%, 95% confidence interval 3-47, p = 0.019]. The overall incidence of complications such as nausea, vomiting, dry mouth, flushing, dizziness, and blurred vision was comparable between the two groups., Conclusions: Chlorpheniramine administration significantly reduces the incidence and severity of CRBD in the patients undergoing TURBT., Trial Registration: KCT0004880 ( https://cris.nih.go.kr/ )., (© 2021. Japanese Society of Anesthesiologists.)

Chlorpheniramine (CPM) is an illegal additive found in herbal teas and health foods, and its excessive intake can cause health problems. In this study, a CPM monoclonal antibody (mAb) was developed based on a new type of hapten. The mAb was found to belong to the IgG2b subclass and showed high sensitivity and specificity when used in ELISA, with a half-maximal inhibitory concentration (IC 50 ) of 0.98 ng mL -1 and cross-reactivity (CR) values below 1.8% when compared to antiallergic drugs. Based on the mAb produced, a fluorescent microsphere-based immunochromatographic strip assay (FM-ICS) and a gold nanoparticle-based immunochromatographic strip assay (GNP-ICS) were developed for the rapid and sensitive detection of CPM in herbal tea samples. Under optimal conditions, the cut-off values for the FM-ICS and GNP-ICS were 10 ng mL -1 and 100 ng mL -1 , respectively, in herbal tea samples. The FM-ICS exhibited a higher sensitivity than GNP-ICS, but both could produce results within 15 min. In addition, a variety of high-throughput rapid immunoassay formats could be implemented based on this mAb for use as a convenient and reliable tool for the determination of CPM exposure in foods and the environment.

Currently, there is no systematic approach available for the validation, quantitative assessment, and troubleshooting for the in-situ fiber optic/bathless dissolution system (FODS). In this report, a dissolution protocol was developed and validated for a model product, chlorpheniramine maleate (CPM) 4 mg IR tablets. Dissolution runs were conducted at 37 ± 0.2 °C using a USP apparatus II, at 50 rpm in 500 mL of 0.01 N hydrochloric acid. The dissolution system was validated for linearity, accuracy, precision, specificity, and robustness analogously to an HPLC method validation. The linearity determination method was developed using five concentration levels between 25-125 % of the expected concentration, while for accuracy, 80 %, 100 %, and 120 % levels were used, and precision was determined using six runs at the 100 % level. Probe sampling depth, orientation, analytical wavelength, and paddle speed were varied to evaluate the robustness of the system tested. Method equivalence was established by comparing the dissolution results from FODS and the traditional dissolution method using UV spectrophotometry. Based on the statistics generated using the dissolution tests, the results are linear, accurate, precise, and specific. Robustness testing demonstrates that small changes in operating conditions did not significantly change the result. No significant difference in the amount dissolved at Q-timepoint was observed between FODS and traditional testing. Therefore, the FODS is a suitable alternative to traditional dissolution for CPM immediate-release tablets (many other drug products have been tested in the laboratory, and reports are in preparation). Additionally, the current work discusses problems related to media preparation, probe sensitivity, and excipient effects on data collected using FODS. The instrument-specific artifacts and data analysis problems are addressed and troubleshooting with possible solutions to eliminate or mitigate the errors. Although the FODS method was developed and evaluated using CPM in 500 mL dissolution volume, the dissolution method using a more common pharmacopoeial dissolution volume, i.e., 900 mL, was used to demonstrate the troubleshooting experiments for the drug products requiring 900 mL dissolution media., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Jellies for oral administration have been suggested as alternative dosage forms to conventional tablets for improved palatability and compliances for pediatric and geriatric patients. To evaluate the effect of jelly formulation on the bioavailability of cold medicines, two types of jellies were prepared for a fixed-dose combination of acetaminophen (AAP), chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DMH), and dl-methylephedrine hydrochloride (MEH). Jelly-S and Jelly-H were fabricated using carrageenan and locust bean gum in the absence and presence of xanthan gum, respectively. In vitro dissolution and in vivo absorption of the four drugs in the jellies were compared with other conventional formulations, a syrup and two types of immediate-release (IR) tablets with different hardness, Tablet-S (15 kPa) and Tablet-H (20 kPa). All the formulations exhibited more than 80% dissolution rate within 2 h even though the syrup, Jelly-S, and Tablet-S showed higher 30-min dissolution compared to Jelly-H and Tablet-H. The dissolution rates from the jellies decreased with increasing pH, which resulted in the slowest dissolution in pH 6.8 compared to the syrup and IR tablets. When administered orally to beagle dogs, all five formulations were determined not to be bioequivalent. However, Jelly-S and Jelly-H showed 0.82-1.05 of the geometric mean ratios (GMRs) of AUC 0-t for all four drugs compared to the syrup suggesting comparable absorption. In two IR tablets, GMRs of AUC 0-t were in a range of 0.55-0.95 indicating a tendency of lower absorption than the syrup and jellies. In conclusion, jelly can be a patient-centered formulation with comparable bioavailability to syrup.

Chlorpheniramine is a pharmaceutical widely used and found in water environments. Besides hormone disruption and adverse environmental effects, chlorpheniramine forms carcinogenic nitrosamines during disinfection. We have demonstrated previously the efficient adsorption of chlorpheniramine from aqueous solution onto graphene oxide-magnetite composite (GO-Fe 3 O 4 ). The present study focused on the elimination of chlorpheniramine and the formation of nitrosamine byproducts during reaction with H 2 O 2 over GO-Fe 3 O 4 catalyst. The effects of the morphology of GO-Fe 3 O 4 in terms of iron fraction, pH, concentrations of H 2 O 2 and organic matters on chlorpheniramine removal in the GO-Fe 3 O 4 -H 2 O 2 system were investigated. Chlorpheniramine was efficiently removed at pH 9 when GO-Fe 3 O 4 had a higher micropore volume and surface area. Kinetics study showed that both oxidation (k = 5.1(±0.2) × 10 -3 (mg g -1 ) -1  min -1 ) and adsorption reactions (k = 2.7(±0.1) × 10 -3 (mg g -1 ) -1  min -1 ) fitted well with the second-order kinetics model. The adsorption sites on the GO-Fe 3 O 4 surface could be different from those involved during catalytic oxidation. Chlorpheniramine removal decreased by 44.9% in the 5th cycle without regeneration due to the structural fracture of GO-Fe 3 O 4 . A tentative pathway of chlorpheniramine degradation and nitrosamine formation by GO-Fe 3 O 4 -H 2 O 2 was proposed. GO-Fe 3 O 4 was an adsorbent and effective catalyst in chlorpheniramine degradation by H 2 O 2 that exhibited limited nitrosamine formation at moderate reaction time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background: This study sought to assess the cutaneous (peripheral) analgesic effects of antihistamine chlorpheniramine, compared with the long-lasting local anesthetic bupivacaine., Methods: After chlorpheniramine and bupivacaine were subcutaneously injected under the dorsal skin of the rats, the cutaneous analgesia effect was quantitatively evaluated by scoring the number to which the animal failed to react (cutaneous trunci muscle reflex). The quality and duration of chlorpheniramine and bupivacaine on infiltrative cutaneous analgesia were compared., Results: We revealed that subcutaneous chlorpheniramine, as well as the local anesthetic bupivacaine elicited cutaneous analgesia in a dosage-dependent manner. Based on their ED 50 s (50% effective doses), the relative potency was found to be chlorpheniramine [1.13 (1.05-1.22) μmol] < bupivacaine [0.52 (0.46-0.58) μmol] (p < 0.01). When comparing the ED 25 s, ED 50 s and ED 75 s, full recovery time induced by chlorpheniramine was longer (p < 0.01) than that induced by bupivacaine., Conclusions: Our preclinical data demonstrated that both chlorpheniramine and bupivacaine dose-dependently provoked the cutaneous analgesic effects. Chlorpheniramine with a more prolonged duration was less potent than bupivacaine in inducing cutaneous analgesia.

Background: Chlorpheniramine (CPA), thanks to its relatively lower side effects, is a widely prescribed medicine for alleviating allergic symptoms as well as some medical emergencies. Owning to this extensive use, many efforts have been directed to measure chlorpheniramine both in vivo and in vitro. High performance liquid chromatography (HPLC), both normal and reverse phase, as well as spectrochemical and electrochemical methods are analytical approaches which have been extensively exploited for determination of CPA. Among them, electrochemical techniques have found elegant place for analysis of CPA due to simplicity, sensitivity and ease of instrumentation., Methods: Herein, we have reported the preparation and characterization of a biosensor by immobilization of double-stranded DNA on the surface of overoxidizedpolypyrrole-reduced graphene oxide modified pencil graphite electrode (ds-DNA-PPyox/RGO/PGE) as well as its novel usability in measurement of chlorpheniramine (CPA). Scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), UV-Vis spectroscopy and differential pulse voltammetry (DPV) were exploited in order to characterize and evaluate the performance of the proposed biosensor., Results: Final results showed that proposed strategy for modification of PGE introduces an ultra-sensitive biosensor for CPA which offers the best detection limitamong all previously reported electrochemical sensors for CPA. Taking advantage of this biosensor for determination of CPA, a wide linear dynamic range from 0.05 to 200 μM, and a low limit of detection 0.023 μM were obtained by using DPV method. Usability of this biosensor was also confirmed by determination of CPA in tablet and spiked urine samples., Conclusions: Overoxidized polypyrrole-reduced graphene oxide offered a suitable substrate for immobilization of ds-DNA by which a new biosensor for determination of CPA was fabricated. Proposed biosensor can successfully be used for determination of CPA in urine samples taking advantage of electroanalytical methods. Graphical abstract.

Studying the origin of opiate and/or opiate metabolites in individual urine specimens after consumption of cold syrups is vital for patients, doctors, and law enforcement. A rapid liquid chromatography-tandem mass spectrometry method using "dilute-and-shoot" analysis without the need for extraction, hydrolysis and/or derivatization has been developed and validated. The approach provides linear ranges of 2.5-1000 ng mL -1 for 6-acetylmorphine, codeine, chlorpheniramine, and carbinoxamine, 2.5-800 ng mL -1 for morphine and morphine-3-β-d-glucuronide, and 2.5-600 ng mL -1 for morphine-6-β-d-glucuronide and codeine-6-β-d-glucuronide, with excellent correlation coefficients (R 2 > 0.995) and matrix effects (< 5%). Urine samples collected from the ten participants orally administered cold syrups were analyzed. The results concluded that participants consuming codeine-containing cold syrups did not routinely pass urine tests for opiates, and their morphine-codeine concentration ratios (M/C) were not always < 1. In addition, the distribution map of the clinical total concentration of the sum of morphine and codeine against the antihistamines (chlorpheniramine or carbinoxamine) were plotted for discrimination of people who used cold syrups. The 15 real cases have been studied by using M/C rule, cutoff value, and distribution map, further revealing a potential approach to determine opiate metabolite in urine originating from cold syrups.

In this study, a series of novel ethylenediamine compounds were obtained by structural modification of the lead compounds with thonzylamine, and using the principle of modifying by bioisostere formation and modification with alkyl groups. In vitro assay, the biological activities showed that the target compounds have good properties in inhibiting mast cell degranulation and releasing histamine and β-aminohexidase, such as the compounds 5c, 5g, 5k, 5l and 5o, especially of compound 5k to mast cell degranulation is IC 50  = 0.0106 ± 0.001 μmol⋅L -1 , histamine release was IC 50  = 0.0192 ± 0.005 μmol⋅L -1 and β-hexosaminidase release was IC 50  = 0.0455 ± 0.002 μmol⋅L -1 in vitro. At the same time, in vivo biological activities assay results showed that have a good Histamie induce bronchospasm effect with relatively long duration and good protective effect in vivo, among which the protective effect of compound 5k was 79.74 ± 0.30%, compounds 5c, 5g, 5k, 5l and 5o could inhibit the capillary permeability of increasing which were caused by histamine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The deletion of the distal 7q region is a rare chromosomal syndrome characterized by wide phenotypic manifestations including growth and psychomotor delay, facial dysmorphisms, and genitourinary malformations., Methods: We describe a 6-year-old child with a 12-Mb deletion of the region 7q35q36.3., Results: Among the deleted genes, two genes have cardiac implications: PRKAG2 (OMIM #602743), associated with hypertrophic cardiomyopathy, cardiac conduction disease, and sudden death, and KCNH2 (OMIM #152427), coding for a cardiac potassium channel involved in long QT syndrome, unmasked by the chlorpheniramine treatment. At same time, the SHH gene (OMIM #600725), encoding sonic hedgehog, a secreted protein that is involved in the embryonic development, is deleted., Conclusion: Our report underlines potential cardiac complications linked to the common pharmacological treatment in this rare multiorgan and proteiform disease., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Chlorpheniramine is a pharmaceutical pollutant and a precursor of carcinogenic nitrosamines during disinfection/oxidation. In our previous study, graphene oxide coated with magnetite (GO-Fe 3 O 4 ) was capable of removing chlorpheniramine in deionized water by adsorption. This study investigated the removal of chlorpheniramine and its nitrosamine formation potentials (FPs) by adsorption onto magnetic GO-Fe 3 O 4 , with respect to the influence by using real municipal wastewaters as the background. In the results, the adsorption performances of chlorpheniramine in wastewaters decreased in the order: GO-Fe 3 O 4 suspension > GO-Fe 3 O 4 particles > activated carbon. Chlorpheniramine adsorptions on GO-Fe 3 O 4 particles and activated carbon were reduced by using real wastewaters as the background, whereas chlorpheniramine adsorption on GO-Fe 3 O 4 suspension was enhanced due to the effects of surface charge on GO-Fe 3 O 4 and ionic strength variation in water. The fittings of adsorption isotherms indicated that the wastewater background reduced the surface heterogeneity of GO-Fe 3 O 4 suspension and improved the adsorption performance. Appreciable removal efficiencies of NDMA and other nitrosamine FPs were observed when GO-Fe 3 O 4 particles were added in real wastewaters. However, when chlorpheniramine was present in wastewaters, chlorpheniramine adsorption and degradation reaction simultaneously occurred on the surface of GO-Fe 3 O 4 , increasing NDMA and other nitrosamine FPs in wastewaters after GO-Fe 3 O 4 addition for chlorpheniramine adsorption. The assumption was further demonstrated by observing the NDMA-FP increase during chlorpheniramine adsorption on GO-Fe 3 O 4 in deionized water. GO-Fe 3 O 4 is a potential adsorbent for chlorpheniramine removal. Nevertheless, the low treatment efficiencies at high doses limit its application for nitrosamine FP adsorptions in real wastewaters.

The dopaminergic and histaminergic systems are the first to appear during the development of the nervous system. Through the activation of H 1 receptors (H 1 Rs), histamine increases neurogenesis of the cortical deep layers, while reducing the dopaminergic phenotype (cells immunoreactive to tyrosine hydroxylase, TH + ) in embryo ventral mesencephalon. Although the function of histamine in neuronal differentiation has been studied, the role of H 1 Rs in neurogenesis has not been addressed. For this purpose, the H 1 R antagonist/inverse agonist chlorpheniramine was systemically administered (5 mg/kg, i.p.) to pregnant Wistar rats (gestational days 12-14, E12-14), and control and experimental embryos (E14 and E16) and pups (21-day-old) were evaluated for changes in nigro-striatal development. Western blot and immunohistochemistry determinations showed a significant increase in the dopaminergic markers' TH and PITX3 in embryos from chlorpheniramine-treated rats at E16. Unexpectedly, 21-day-old pups from the chlorpheniramine-treated group, showed a significant reduction in TH immunoreactivity in the substantia nigra pars compacta and dorsal striatum. Furthermore, striatal dopamine content, evoked [ 3 H]-dopamine release and methamphetamine-stimulated motor activity were significantly lower compared to the control group. These results indicate that H 1 R blockade at E14-E16 favors the differentiation of dopaminergic neurons, but hampers their migration, leading to a decrease in dopaminergic innervation of the striatum in post-natal life.

Influenza A viruses (IAV) comprise some of the most common infectious pathogens in humans, and they cause significant mortality and morbidity in immunocompromised people as well as children and the elderly. After screening an FDA-approved drug library containing 1280 compounds by cytopathic effect (CPE) reduction assay using the Cell Counting Kit-8, we found two antihistamines, carbinoxamine maleate (CAM) and S-(+)-chlorpheniramine maleate (SCM) with potent antiviral activity against A/Shanghai/4664T/2013(H7N9) infection with IC 50 (half-maximal inhibitory concentration) of 3.56 and 11.84 μM, respectively. Further studies showed that CAM and SCM could also inhibit infection by other influenza A viruses, including A/Shanghai/37T/2009(H1N1), A/Puerto Rico/8/1934(H1N1), A/Guizhou/54/1989(H3N2), and one influenza B virus, B/Shanghai/2017(BY). Mice were challenged intranasally with A/H7N9/4664T/2013 (H7N9) virus and intraperitoneally injected with CAM (10 mg/kg per day) or SCM (1 mg/kg per day) for 5 days. CAM or SCM (10 mg/kg per day) were fully protected against challenge with A/Shanghai/4664T/2013(H7N9). The results from mechanistic studies indicate that both could inhibit influenza virus infection by blocking viral entry into the target cell, the early stage of virus life cycle. However, CAM and SCM neither blocked virus attachment, characteristic of HA activity, nor virus release, characteristic of NA activity. Such data suggest that these two compounds may interfere with the endocytosis process. Thus, we have identified two FDA-approved antihistamine drugs, CAM and SCM, which can be repurposed for inhibiting infection by divergent influenza A strains and one influenza B strain with potential to be used for treatment and prevention of influenza virus infection.

Purpose To evaluate premedication protocols involving administration of antihistamine and multidose corticosteroid that have been widely used in prevention of recurrent hypersensitivity reactions (HSRs) to iodinated contrast media (ICM); an evidence-based optimal preventive strategy customized for patients with mild cases has not yet been established. Materials and Methods The outcomes of patients with mild HSR who subsequently underwent contrast material-enhanced computed tomography (CT) between January 2012 and December 2015 were analyzed. For premedication, 4 mg of chlorpheniramine was intravenously administered 30 minutes prior to reexposure to ICM. Logistic regression with generalized estimating equations was used to determine the relationship between premedication and recurrence rate. Results A total of 1178 patients with mild immediate HSR were reexposed to ICM 3533 times. Among these patients, 1056 patients experienced allergylike reactions and 122 patients developed gastrointestinal reactions. With reexposure to the culprit agent without premedication, the recurrence rate was 31.1% (85 of 273 examinations). The recurrence rate decreased to 12% (105 of 872 examinations; P < .001) by only changing the culprit agent and to 7.6% (148 of 1947 examinations; P < .001) by using the combination of changing the ICM and antihistamine premedication. Changing the ICM plus antihistamine premedication was also helpful in reducing the recurrence of gastrointestinal symptoms from 16.1% to 1.8% (P = .020). However, despite changing of the ICM, some combinations of ICM did not show a prophylactic effect. Conclusion A combination of changing the culprit agent and antihistamine premedication resulted in the best preventive outcome for patients with mild immediate HSR. The optimal choice of substitute ICM could be individualized according to the culprit agent., (© RSNA, 2018 Online supplemental material is available for this article .)

Objectives: In this study, we aimed to develop and optimize an anti-allergic cream containing dexamethasone and chlorpheniramine using the design of experiments (DoE) method. The optimized product was investigated for its physicochemical properties and in vivo therapeutic effects in rabbits., Materials and Methods: The creams were formulated using the simple mixing process, which was optimized by the Design Expert software. The products were then evaluated the properties such as pH, skin diffusion profile, short-term stability, qualitative, and assay, using the newly validated UV-Vis spectrophotoscopy quantitative method. In vivo efficacy tests in rabbits of the best products were compared with the marketed Phenergan ® (promethazine 2%)., Results: The UV-Vis method used to simultaneously determine the amount of both dexamethasone and chlorpheniramine was successfully developed and validated. Using the DoE method, it was clear that the release profile of dexamethasone depended on the amount of sodium lauryl sulfate, propylene glycol, and DMSO. In contrast, only DMSO affected the release pattern of chlorpheniramine. The best formulation was optimized by the software. The product showed acceptable parameters in pH (5.7±0.1), short-term stability over 10 days, and skin diffusion profiles of 20.47±1.25% and 4.92±0.42% after 40 min for dexamethasone and chlorpheniramine, respectively. In addition, the product demonstrated no observable inflammatory response in the experimental animals. Also, it illustrated 2-fold better anti-allergic efficacy than the marketed product (i.e., 27.2 compared with 43.4 min in the recovery time)., Conclusion: We were successful in developing and optimizing an anti-allergic cream containing dexamethasone and chlorpheniramine. The best product satisfied all required parameters. Interestingly, our product showed higher efficacy than Phenergan ® . These results can be a background for further clinical trials., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2018 Turk J Pharm Sci, Published by Galenos Publishing House.)

Background: Cetirizine has been shown to be effective for relief of seasonal allergic rhinitis (SAR) symptoms. Allergic rhinitis symptoms have been reported to have circadian variations, with symptoms tending to be most bothersome overnight and in the morning., Objective: To evaluate the effects of different cetirizine dosing schedules in comparison to twice daily (BID) chlorpheniramine and placebo on SAR symptoms at 12 and 24 hours postdose., Methods: Study 1 subjects received cetirizine 10-mg once daily in the morning (QAM), cetirizine 10-mg once daily at bedtime (QHS), cetirizine 5-mg twice daily, or placebo. Study 2 subjects received cetirizine 5-mg QAM, cetirizine 10-mg QHS, chlorpheniramine 8-mg BID, or placebo. The primary end point was total symptom severity complex (TSSC); TSSC was the sum of symptom severity ratings averaged over the 2-week study period. Post hoc analyses of reflective symptom severity assessed in the morning (TSSC AM ) and in the evening (TSSC PM ) were conducted to evaluate cetirizine's effects at 12 and 24 hours postdose., Results: In study 1, subject- and investigator-assessed TSSC was significantly lower in all cetirizine groups versus placebo ( P ≤ .003). In study 2, subject-assessed TSSC was significantly lower in all cetirizine groups versus placebo ( P ≤ .04) and was numerically lower for investigator-assessed TSSC. Post hoc analyses demonstrated that cetirizine significantly improved TSSC AM at 12 and 24 hours postdose versus placebo in both studies regardless of dosing schedule. TSSC PM significantly improved at 12 and 24 hours postdose in all study 1 cetirizine groups versus placebo. In study 2, versus placebo, TSSC PM significantly improved at 12 hours postdose in cetirizine 5-mg QAM group and numerically improved at 24 hours postdose in cetirizine 10-mg QHS group., Conclusion: Regardless of dosing regimen, cetirizine demonstrates effective 24-hour relief of SAR symptoms, particularly on TSSC AM , which assesses overnight and early morning symptom control.

Two pediatric studies characterized brompheniramine and chlorpheniramine pharmacokinetics in a total of 72 subjects, aged 2 to 17 years. A single age-/weight-based oral dose, ranging from 1 to 4 mg, was administered with 2 to 6 oz of water at least 2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed using high-pressure liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods; relationships with age were assessed using linear regression. Results indicated that for brompheniramine and chlorpheniramine, C max was similar across age groups, although it tended to occur earlier in the youngest group. AUC was ∼15% to 30% higher in the oldest age group. As expected, CL o and V z /F increased with age; however, following allometric scaling, no age-related differences existed. Because the increase with age for both parameters was similar, no age-related differences in t 1/2,z existed (∼15 hours). Overall, the single doses were well tolerated. Sedation was the most common reported AE and appeared to be more prevalent in the 2- to 5-year-old group. Overall, these results indicate that an age/weight dosing nomogram using a 4-fold range of doses achieves similar C max and AUC., (© 2017, The American College of Clinical Pharmacology.)

This study investigated the influence of the histamine H 1 receptor antagonists, chlorpheniramine (CHL) and pyrilamine, on the analgesic effects of acupuncture in mice. Nociceptive response was evaluated by the acetic acid-induced abdominal writhe test. Electroacupuncture (EA) at bilateral ST36 reduced the manifestations of acetic acid-induced abdominal writhing, whereas needle insertion without electrostimulation had no such effect. Notably, EA treatment was not associated with any analgesic effects in mice pretreated with naloxone. Low doses of CHL (0.6[Formula: see text]mg/kg; p.o.) or pyrilamine (2.5[Formula: see text]mg/kg; i.p.) as monotherapy did not affect acetic acid-induced abdominal writhing. However, when each agent was combined with EA, acetic acid-induced abdominal writhing was reduced by a greater extent when compared with EA alone. Interestingly, the effects of CHL on acupuncture analgesia were not completely reversed by naloxone treatment. Acetic acid induced increases of phospho-p38 expression in spinal cord, as determined by immunofluorescence staining and Western blot analysis. These effects were attenuated by EA at ST36 and by low doses of histamine H 1 receptor antagonists, alone or in combination. Our findings show that relatively low doses of histamine H 1 receptor antagonists facilitate EA analgesia via non-opioid receptors. These results suggest a useful strategy for increasing the efficacy of EA analgesia in a clinical situation.

Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E) 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H 1 receptor (H 1 R) which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H 1 R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2) and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H 1 R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H 1 R expression by qRT-PCR and Western blot and, finally, we tested H 1 R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers) and partially reverted the increased level of MAP2 protein at E14, concluding that H 1 R have an important role in the increased neurogenesis within the dorsal telencephalon of embryos from diabetic rats. This study opens new perspective on the participation of HA and H 1 R receptor in early corticogenesis in health and disease.

There is a crosstalk between mood disorders and oxidative stress. Chlorpheniramine (CPA), a first generation antihistamine, is hypothesized to have an anxiolytic role at high doses; however, its antidepressant and antioxidant roles have not previously been investigated. The aim of the current study was to evaluate the antidepressant and anxiolytic effects of CPA treatment in association with nitric oxide (NO) and super oxide dismutase (SOD) activity in a mouse model of anxiety. BALB/c mice were divided into unstressed (naïve), control, and CPA- (0.5 mg/kg) and escitalopram- (ESC; 10 mg/kg) treated groups for 3 weeks. Subsequently, they were immobilized for 6 h and subjected to behavioural paradigms as follows: The open field test, the elevated plus maze (EPM) and the forced swim test to investigate motor function, anxiety and depression, respectively. The mice were sacrificed and serum was obtained to detect NO and SOD activity. Compared with the control group, the CPA-treated group demonstrated an antidepressant effect similar to that of the ESC-treated group. In addition, CPA prevented stress-induced NO without affecting SOD activity. CPA did not improve anxiety-like behaviour in the EPM, nor did it improve stress-induced locomotion and rearing, as demonstrated by the OFT. Thus, to the best of our knowledge, this is the first study to evaluate the antidepressant role of CPA in association with NO metabolism. However, further studies are required to elucidate the underlying mechanism.

Microglial NADPH oxidase is a major source of toxic reactive oxygen species produced during chronic neuroinflammation. Voltage-gated proton channel (H V 1) functions to maintain the intense activity of NADPH oxidase, and channel inhibition alleviates the pathology of neurodegenerative diseases such as ischemic stroke and multiple sclerosis associated with oxidative neuroinflammation. Antagonists of histamine H 1 receptors have beneficial effects against microglia-mediated oxidative stress and neurotoxicity. We examined the effects of the H 1 antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells recorded using the whole-cell patch clamp technique. Diphenhydramine and chlorpheniramine reduced the proton currents with almost the same potency, yielding IC 50 values of 42 and 43μM, respectively. Histamine did not affect proton currents, excluding the involvement of histamine receptors in their action. Neither drug shifted the voltage-dependence of activation or the reversal potential of the proton currents, even though diphenhydramine slowed the activation and deactivation kinetics. The inhibitory effects of the two antihistamines on proton currents could be utilized to develop therapeutic agents for neurodegenerative diseases and other diseases associated with H V 1 proton channel abnormalities., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Metoclopramide is a commonly used anti-emetic drug known to cause extrapyramidal symptoms as adverse effects, amongst which are dystonic reactions. These reactions are more frequent at high doses of metoclopramide, in female patients, children and adults less than 30 years of age. We hereby present the case of a 16 year old female who had dystonic reactions from metoclopramide, highlighting its unpredictable nature and the shortcomings of the management in resource-limited settings., Case Presentation: A 16 year old female Muslim from the Extreme North of Cameroon with no significant past history, was treated for severe malaria and associated refractory vomiting using intravenous quinine and metoclopramide respectively. She developed dystonic reactions after being administered her second dose of metoclopramide. The drug was discontinued and she was administered 8 mg of chlorpheniramine by mouth. Her symptoms resolved after 4 h. She was discharged 2 days later with no further complaints., Conclusions: Metoclopramide causes dystonic reactions which are often unpredictable and is frequently prescribed by health providers. This creates an environment of anxiety for the patient and the caregiver, and can result in life threatening consequences. Patients on metoclopramide should be monitored closely to detect these reactions early, and health facilities should be equipped to cope with the adverse effects before administration.

This study investigated the effects of bilateral intraamygdalar microinjections of PNU-282987, a nicotinic cholinergic agonist, on anxiety and the reversal of amnesia induced by chlorpheniramine (CPA), an H1 histaminergic antagonist, in mice subjected to the elevated plusmaze (EPM). Two experiments were performed with seventy-nine adult male Swiss mice. The isolated microinjections of PNU-282987 did not produce effects on emotional memory; however, the combined microinjections of PNU-282987 and CPA were able to reverse the deficit in memory induced by CPA (ANOVA, p<0.05). Taken together, these results suggest that intraamygdalar injections of PNU-282987 did not induce effects on anxiety and emotional memory per se; however, concurrent microinjections of PNU-282987 and CPA-reverse amnesia induced-CPA which is suggestive of an interaction between the histaminergic and cholinergic systems in the modulation of emotion memory acquisition in mice., (Copyright © 2016 Elsevier Inc. All rights reserved.)