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An stability indicating HPLC methodology for the concurrent estimation of Tricholine citrate (TRC) and Cyproheptadine hydrochloride (CYH) in syrup dose and bulk using Waters column reverse phase C18 (5 µm, 250 mm and 4.6 mm) as stationary phase and 0.1M Na2HPO4 of pH 4.5 and acetonitrile in proportion of 60:40 (v/v) at flow of 1.0 ml/min rate as mobile phase was reported. The linear scales were 275-825 μg/ml for TRC and 2-6 μg/ml for CYH with correlation coefficients of 0.9999 for TRC and 0.9997 for CYH. Followed ICH Q2(R1) strategies for validating the suggested method for precision, sensitivity, robustness, specificity, selectivity and accuracy. The measures of LOD and LOQ are 0.023 µg/ml and 0.079 µg/ml for CYH, while for TRC it was 0.565 µg/ml and 1.885 µg/ml, respectively. The precision measures for CYH and TRC were 0.073 and 0.212 relative measured deviation percentage, respectively. The accuracy measures for CYH and TRC were 99.40% and 99.09% mean assay percentiles, respectively. Recovery percentiles measures of CYH and TRC were ranged between 99.48% to 100.35% and 100.38% and 100.41%, respectively. While in degradation investigation, peaks of degraded products are very well differentiated from TRC and CYH peaks suggesting the specificity and stability of suggested methodology. The results permit the application of the proposed stability indicating HPLC methodology in syrup dose forms.

This work presents a sensitive, accurate and selective RP-HPLC method for simultaneous determination of cyproheptadine HCl (CPH), its impurity B (dibenzosuberone) and CPH oxidative degradation product (10,11-dihydroxy-dibenzosuberone) in bulk powder and in pharmaceutical formulation. The RP-HPLC method depends on isocratic elution using C8 column and mobile phase consisting of 0.05 M KH2PO4 buffer:methanol (35:65, v/v, pH = 4.5) at a flow rate of 2 mL/min, and the eluant was monitored at 245 nm. Good resolution was obtained with tR values of 3.05, 7.54 and 6.17 min for CPH, impurity and oxidative degradate, respectively. The proposed method has been validated as per ICH guidelines using pure forms of CPH, its impurity and degradation product in pharmaceutical formulation with an accuracy of 100.48, 100.16 and 100.11, respectively. Additional spiking experiments yielded an accuracy of 100 ± 1.6%. Repeatability and intermediate precision results indicated acceptable low

Failure to thrive (FTT) impairs the expected normal physical growth of children. This study aimed to evaluate the effects of cyproheptadine hydrochloride on growth parameters in prepubertal children with FTT. The medical records of prepubertal children who were newly diagnosed with FTT at China Medical University Hospital between 2007 and 2016 were retrospectively examined. The patients were divided into two groups depending on whether they had (T-group) or had not (NT-group) received cyproheptadine hydrochloride (0.3 mg/kg daily) for at least 14 days. The mean length of the treatment period was 97.22 days (range: 14–532 days). Weight, height, and body mass index were adjusted for age using the median values in the growth charts for Taiwanese boys and girls as the reference. A total of 788 patients aged 3–11 years were enrolled, 50 in the T-group and 738 in the NT-group. No statistically significant difference in the median age-adjusted weight value was noted between the T-group and NT-group during the follow up period. In the T-group, age-adjusted weight and body mass index were inversely associated with age (P P P = 0.026, P = 0.04). Our findings underscore the positive association between cyproheptadine hydrochloride treatment and weight gain among prepubertal children. Further prospective clinical studies with a. longer and consistent treatment course is warranted.

Background The voltage-gated K+-channel Kv11.1 has a central role in cardiac repolarization. Blockage of Kv11.1 has been linked to severe cardiovascular side effects, such as acquired long QT syndrome (aLQTS), torsade de pointes arrhythmia and sudden cardiac death (SCD). Kv11.1 is susceptible to unspecific drug interactions due to the presence of two aromatic amino acids residing in the inner vestibule of the pore. These aromatic residues are also present in the equine orthologue of Kv11.1. This suggests that equine Kv11.1 may also be prone to high-affinity block by a range of different chemical entities, which potentially could cause severe cardiac side effects and SCD in horses. Aim To screen a series of commonly used drugs in equine medicine for interaction with Kv11.1. Methods High-throughput screening of selected compounds on human Kv11.1 expressed in a mammalian cell line was performed using an automated patch clamp system, the SyncroPatch 384PE (Nanion Technologies, Munich, Germany). Results were validated on equine Kv11.1 expressed in CHO-K1 cells by manual patch clamp. Results Acepromazine maleat (IC50 = 0.5 μM) trimethoprim (IC50 = 100 μM), diphenhydramine hydrochloride (IC50 = 2 μM) and cyproheptadine hydrochloride (IC50 = 1.84 μM) inhibited equine Kv11.1 current at clinically relevant drug concentrations. Conclusion The results suggest that drug interaction with Kv11.1 can occur in horses and that some drugs potentially may induce repolarization disorders in horses.

Cyproheptadine hydrochloride(CH)- and dexamethasone-induced obsessive-compulsive symptomatology with suicide is extremely rare. We describe the case of a 20-year-old lean male who developed obsessive-compulsive symptoms and suicidality within a week of the use of CH and dexamethasone. There was complete resolution of symptoms after stopping the offending agent. Ashort trial of selective serotonin reuptake inhibitor was given for the rapid improvement of symptoms.

Background: For the first time, the inhibitory effects on the human salivary alpha-amylase activity of the anti-inflammatory drugs indomethacin, diclofenac sodium, ketoprofen, diclofenac potassium, diclofenac, triamcinolone acetonide, and the antihistamine drugs levocetirizine dihydrochloride, desloratadine, cycloheptadine hydrochloride, have been investigated to confirm the other properties of these drugs. Objective: This study aimed to determine the effect of nine known drugs on human salivary α-amylase in vitro and the nature of interactions with structure-activity relationship using molecular docking experiments. Methods: The inhibition of human salivary alpha amylase by the six anti-inflammatory and three antihistamine drugs has been carried out using the new method that has been proved in our previous work. Molecular docking has been achieved for the first time for these drugs using the Auto- Dock Vina program. Results: Cyproheptadine hydrochloride presented the highest inhibitory activity against α-amylase with IC50=0.7 mg/ml, while the other drugs showed weak activities (IC50 > 2 mg/ml). Conclusion: We conclude that Cyproheptadine hydrochloride, which was studied by docking experiments, exhibited the best inhibitory activity on salivary α-amylase in vitro & in silico.

A sensitive, simple and rapid stability-indicating HPLC method using fluorescence detection was developed for the quantitative determination of the antihistaminic drug cyproheptadine hydrochloride ...

BACKGROUND Cyproheptadine HCl (CyproH) is an appetite-stimulating drug and while it was prescribed for a patient with growth hormone insensitivity syndrome (GHIS) for increasing appetite, his height growth was surprisingly increased. Therefore, the aim of this study was to investigate the effect of CyproH on growth parameters of the patients with GHIS. PATIENTS AND DESIGN Twenty patients were enrolled in two prospective cohorts at two different times. Fifteen cases were observed for 1.17 ± 1.3 years without treatment (observation period, OP). Then, CyproH was administered for 2.2 ± 2.7 years (treatment period, TP), and growth parameters were compared within these two periods. Five patients who did not receive any treatment for 1-8.24 years (4 ± 2.9) were the control group. RESULTS Height velocity (HV) increased from 1.88 ± 0.7 to 6.1 ± 0.8 cm/year and HV-SDS reached from -4.5 ± 0.74 to -0.21 ± 1.2 in OP and TP, respectively (P

Simple and sensitive first derivative synchronous spectrofluorimetric method was developed for the determination of cyproheptadine hydrochloride in presence of its oxidative degradation product. The method was based on measuring the synchronous fluorescence of the drug in water at Δλ of 120 nm in the presence of a sodium dodecyl sulphate as a micellar system. The peak amplitude of the first derivative spectra was measured at 418 nm for the drug. The different experimental parameters affecting the synchronous fluorescence intensity of CYP were studied and optimized. The peak amplitude–concentration plot was rectilinear over the range of 0.1–1.6 µ gmL−1. The limit of detection (LOD) was 0.02 and quantification limit (LOQ) was 0.06 µgmL−1. The proposed method was successfully applied to commercial tablets. Statistical comparison of the results with those of the official method revealed good agreement and proved that there was no significant difference in the accuracy and precision of the two methods.

Background: Cyproheptadine hydrochloride is an antihistaminic drug. Appetite stimulation is one of its secondary effects that can be of advantage in some diseases. In this study we investigated the effect of Cyproheptadine hydrochloride on weight gain in underweight children with anorexia at age group 2 to10 years old. Materials and Methods: In this randomized clinical trial, we selected 2-10 year-old underweight children with anorexia who referred to Ayatollah Mousavi Hospital in Zanjan (Iran), during 2015. One hundred and thirty-six children were allocated at random in two groups. The Cyproheptadine - treated children group were given the drug orally; 0.1 mg/kg/dose three times per day for 8 weeks, while patients in placebo group received placebo with the same dose. After two months, weight gain was compared with the previous values in both groups. Results: In this study, 86 patients (63.2%) were female. The average increase in weight in the cyproheptadine - treated group was significantly higher than in the placebo group (1.08 ± 0.67 kg and 0.22 ± 0.46 kg, respectively) (p=0.005). The average increase height in the Cyproheptadine -treated group was significantly higher than in the placebo group (1.60 ± 0.97 cm, and 0.86 ± 0.85 cm, respectively) (p=0.005). According to the parents of both groups, anorexia in the Cyproheptadine -treated group improved in 100%, and in the placebo group in 52.7%. This difference was statistically significant (p=0.005). No any side effects of Cyproheptadine hydrochloride were observed. Conclusion: According to the finding of our study, there were no serious side effects of Cyproheptadine hydrochloride. Therefore considering the acceptable safety of Cyproheptadine hydrochloride for inducing growth in underweight children, we propose its administration with the aforementioned dose.

Topicality. Cyproheptadine hydrochloride (peritol) is an antihistaminic drug with an antiserotonin effect, which prevents development and facilitates the course of allergic reactions. The drug is characterized by antipruritic, antiexudative, anticholinergic and sedative effects. According to the literature sources, the drug can cause intoxication of the body and the lethal effects of overdosing, self-medication and in cases of suicide. The elaboration of highly sensitive and selective methods for the study of cyproheptadine, suitable for analysis in biological objects is an actual task. Aim. To study the elaboration of algorithm for the directed analysis of cyproheptadine in biological extracts by HPLC and TLC methods. Materials and methods. TLC studies were performed using 16 mobile solvent systems and three types of chromatographic plates. To identify the cyproheptadine were applied universally visualization conditions. HPLC studies were performed on a microcolumn liquid chromatograph “Milichrom A-02” (RPA “EkoNova” Novosibirsk, Russia) in a reversed-phase variant using a metal column with a non-polar sorbent Prontosil 120-5C 18 AQ. Results and discussion. TLC conditions for purifying cyproheptadine from biogenic impurities and its identification have been established. Based on the results of the studies, the behavior of cyproheptadine by the HPLC method was studied. Identification was carried out using retention parameters, spectral relationships, and quantitative determination using the absolute calibration method. The method is validated by parameters – range of linearity, limit of detection and quantitative determination, accuracy and precision. Conclusions. It was established that the most suitable TLC conditions for CTA of cyproheptadine are: mobile solvent systems – ethyl acetate-methanol-25 % solution ammonium hydroxide (85 : 10 : 5), glass plates of firm “Merk” ( Rf cyproheptadine = 0.50-0.55) and methanol, methanol-n-buthanol (60 : 40), Sorbphil-PTCX-AF-A ( Rf cyproheptadine = 0.55-0.58). It is established that the HPLC-method may determine cyproheptadine in a concentration range of 10.0-200.0 µg/ml. The relative uncertainty of the average result is ± 2.05 %. An algorithm for the direct analysis of cyproheptadine in biological extracts by HPLC and TLC methods has been developed.

Background: Cyproheptadine hydrochloride (HCl) is antihistaminic drug which used widely in our country as an appetizer and for weight gain especially for low weight children. Objective: The aims of this study were to assess the effects of cyproheptadine HCl on blood picture including white blood cells count, lymphocytes count, and its effect on the level of different cytokines. Materials And Methods: This is an experimental study conducted at Biotechnology Research Center Laboratory in Alnahrain University from November 2016 to April 2017. It included five groups of albino male mice, these groups were treated separately with four doses of the cyproheptadine drug and fifth as control group; the doses were selected according to the British National Formulary (BNF) 2010 calculated on the base of mice/human deference's in body weight: These are (0.065, 0.092, 0.120, 0.24) mg/mice/day, respectively, with fifth untreated mice group considered as control. Results: The untreated mice (control) lymphocyte count was (4000) cell/ml and the total lymphocytes count increased up to (7014) cell/ml than the normal leading changes in interleukins (ILs) level in different manner, such as decreasing in both IL-6 and IL-10 levels with increasing in IL-12 level and no change in IL-4 level. Conclusion: The current study showed that cyproheptadine HCl may have unwanted side effects, and its abuse may lead to disturbances in white blood cell especially lymphocyte which in turn will affect the immunity of persons taking it, especially in children, since the immune system modulates ILs secretion to face the irritability of drug behavior, that will lead abnormalities in human immune system.

Fluvoxamine is a selective serotonin-reuptake inhibitor, of which IC50 values for serotonin- and noradrenaline-uptake process were reported to be 3.8 and 620 nmol/L, respectively, also known to directly inhibit cardiac Na+, Ca2+, and K+ channels. We characterized microminipig as a laboratory animal by analyzing fluvoxamine-induced cardiovascular and dermatological responses under halothane anesthesia. Fluvoxamine maleate was infused in doses of 0.1, 1, and 10 mg/kg over 10 min with a pause of 20 min (n = 4). The peak plasma concentrations were 35, 320, and 1906 ng/mL, of which free plasma concentrations were estimated as 20, 187, and 1108 nmol/L, respectively. The low and middle doses did not alter any cardiovascular variable. The high dose increased heart rate and mean blood pressure, prolonged QRS width, but shortened QT interval, whereas no significant change was detected in PR interval or QTcF. Moreover, it induced systemic erythema on the skin. Pretreatment of H1/5-HT2A antagonist cyproheptadine hydrochloride sesquihydrate in a dose of 0.3 mg/kg significantly attenuated the fluvoxamine-induced pressor response; but tended to further enhance sinus automaticity, atrioventricular nodal conduction; and ventricular repolarization in addition to intraventricular conduction delay; whereas it markedly suppressed onset of systemic erythema (n = 4). In microminipigs, cardiovascular adverse effects of the high dose may be manifested as a sum of its inhibitory action on the cardiac ionic channels and its stimulatory effects on serotonergic and adrenergic systems, whereas dermatologic reaction can be induced primarily through H1/5-HT2A receptor-dependent mechanism. Thus, microminipigs may be used for analyzing such multifarious adverse events of clinical serotonergic pharmacotherapy.

Data available from the Dryad Digital Repository: < http://dx.doi.org/10.5061/dryad.768vg > (Martín-Gálvez and Soler 2016), The colouration of some traits in nestlings of altricial birds may influence parental food allocation as it may reflect physical condition or hunger. There is increasing evidence of the relationship between colouration of begging traits and nestling performance. However, evidence of the influence of hunger level on nestling colouration is scarce, mainly because of difficulty of distinguishing between the effects of physical condition and hunger levels. Here, we used the appetite stimulant cyproheptadine hydrochloride to increase the sensation of hunger of magpie Pica pica nestlings for eight days and assessed the effect on the colouration of rictal flanges, mouth and body skin. We found that nestlings administered with cyproheptadine had flanges more conspicuous (chromatic visual contrast), more UV coloured and less yellow coloured than their control nestmates. Conversely, mouths of experimental nestlings were more yellow coloured and less UV coloured than controls. Our pharmacological experiment afected the strength of the relationship between body mass and some colour components of body skin (chromatic and achromatic visual contrasts, UV – chroma and yellow – chroma) and of rictal flanges (chromatic visual contrasts, UV – chroma and yellow – chroma), but not for mouth colouration. These results taken together suggest that the effect of the cyproheptadine on nestling colourations is probably mediated by an increase in hunger levels of nestlings for rictal flanges and body skin colourations, and by an increase in physical condition in the case of mouth coloration., Th is research was funded by a postdoctoral fellowship to DM-G from Ministerio de Educación y Ciencia, and by Ministerio de Ciencia e Innovación/FEDER (project CGL2013-48193-C3-1-P)

Cyproheptadine hydrochloride (CYP HCl) {4-(5H-dibenzo[a,d]-cyclohepten-5-ylidene)-1-methylpiperidine hydrochloride} is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local-anesthetic properties. The geometry optimization, Mulliken atomic charges and wavenumber and intensity of the vibrational bands of all of the possible modes of CYP HCl have been calculated using ab initio Hartree–Fock (HF) and density functional theory (DFT) employing the B3LYP functional with the 6-311G(d,p) basis set. We have compared the calculated IR and Raman wavenumbers with experimental data. Quantum-chemical calculations of the geometrical structure, energies, and molecular electrostatic potential and NBO analysis of CYP HCl have been performed using the B3LYP/6-311G(d,p) method. The electric dipole moment ( μ ), static polarizability ( α ) and the first hyperpolarizability ( β ) values of the title compound have been computed using HF and DFT methods. The study reveals that the antihistaminic pharmacological property of CYP HCl has a large β value and, hence, may in general have potential applications in the development of non-linear optical materials. The experimental and calculated results for CYP HCl have also been compared with those for mianserin HCl.

The interaction between cyproheptadine hydrochloride (CYP) and human serum albumin (HSA) was investigated by fluorescence spectroscopy, UV-vis absorption spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and molecular modeling at a physiological pH (7.40). Fluorescence of HSA was quenched remarkably by CYP and the quenching mechanism was considered as static quenching since it formed a complex. The association constants Ka and number of binding sites n were calculated at different temperatures. According to Förster's theory of non-radiation energy transfer, the distance r between donor (human serum albumin) and acceptor (cyproheptadine hydrochloride) was obtained. The effect of common ions on the binding constant was also investigated. The effect of CYP on the conformation of HSA was analyzed using FT-IR, synchronous fluorescence spectroscopy and 3D fluorescence spectra. The thermodynamic parameters ΔH and ΔS were calculated to be -14.37 kJ mol(-1) and 38.03 J mol(-1) K(-1), respectively, which suggested that hydrophobic forces played a major role in stabilizing the HSA-CYP complex. In addition, examination of molecular modeling indicated that CYP could bind to site I of HSA and that hydrophobic interaction was the major acting force, which was in agreement with binding mode studies.

Two simple and rapid titrimetric methods are described for the determination of cyproheptadine hydrochloride (CPH) in pharmaceuticals. The proposed methods are based on the solvent extraction-titration of CPH with two ion association reagents, sodium lauryl sulphate (SLS), (method A), and tetraphenylborate (TPB), (method B). In method A, SLS was used as titrant and the titration was carried out in the presence of dilute sulphuric acid and chloroform using dimethyl yellow as indicator, whereas, in method B, the titrant was TPB and the titration was done in Walpole buffer of pH 4.5 and 1, 2-dichloroethane using tetrabromophenolphthalein ethyl ester as indicator. The proposed procedures give sharp end points as the color of the organic phase changes from yellow to pink in method A, and from red-violet to yellow in method B. The methods are applicable over the ranges of 1.0–20.0 and 2.0–9.0 mg of CPH for method A and method B, respectively. The accuracy and precision of the methods are good. The methods were applied successfully to the determination of CPH in tablets, and the results were in agreement with the label claim and those of the reference method.

One titrimetric and two spectrophotometric methods are described for the determination of cyproheptadine hydrochloride (CPH) in bulk drug and tablets employing N-bromosuccinimide (NBS) as a brominating agent and two dyes, erioglaucine (EG) and meta-cresol purple (MCP) as auxiliary reagents. In titrimetry, a measured excess of NBS is added to an acidified solution of CPH and the unreacted NBS is determined iodometrically. Spectrophotometry involves the addition of a known excess of NBS to CPH in acid medium followed by estimation of residual NBS by reacting with a fixed amount of either erioglaucin and measuring the absorbance at 540 nm (method A) or meta-cresol purple and measuring the absorbance at 630 nm (method B). Titrimetric procedure is applicable over the range of 1.5-15 mg of CPH, and the reaction stoichiometry is found to be 1: 2 (CPH: NBS). The spectrophotometric methods are applicable over the ranges of 0.1-2.0 μg mL-1 (method A) and 0.4-12 μg mL-1 (method B). The molar absorptivities are calculated to be 1.4 × 105 and 2.2×104 Lmol-1cm-1 for method A and method B, respectively, and the corresponding Sandell sensitivity values are 0.0023 and 0.0141 μg cm-2. The limits of detection are calculated and found to be 0.03 and 0.24 μg mL-1 for method A and method B, respectively with corresponding limits of quantification 0.09 and 0.71. The methods were applied to the assay of CPH in tablets, and the results were compared statistically with those of a reference method.

The present study examined the involvement of 5-HT in the ventrolateral orbital cortex (VLO) on descending antinociception and determined which subtypes of 5-HT receptors mediated this effect. This study focused on the effects of 5-HT microinjection in the VLO of lightly anesthetized male rats on the radiant heat-evoked tail flick (TF) reflex, as well as the influence of 5-HT(1A), 5-HT(2), 5-HT(3), and 5-HT(4) receptor subtype antagonists on the effect of 5-HT. Results showed that 5-HT microinjection (2, 5, 10 microg, in 0.5 microl) into the VLO depressed the TF reflex in a dose-dependent manner. Pretreatment with 5-HT receptor antagonists (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190), cyproheptadine hydrochloride (CPT) and 1-methyl-N-(8-methyl-8-azabicyclo[3.2.3]-oct-3-yl)-1H-indazole-3-carboxamide maleate salt (LY-278,584)), specific for 5-HT(1A), 5-HT(2) and 5-HT(3) receptors, respectively, partially reversed the 5-HT-evoked inhibition. In contrast, the 5-HT(4) receptor antagonist, 1-[2-[(methylsulfonyl)-amino]ethyl]-4-piperidinyl]methyl1-methyl-1H-indole-3-carboxylate (GR 113808), had no effect on the inhibition of 5-HT. Microinjections of NAN-190, CPT and LY-278,584 alone into the VLO had no effect on the TF reflex. These results suggest that 5-HT(1A), 5-HT(2) and 5-HT(3), but not 5-HT(4) receptors, are involved in mediating 5-HT-induced antinociception in the VLO. According to different properties and distribution patterns of the 5-HT receptor subtypes on neurons, the possible mechanism of 5-HT activation of the VLO-periaqueductal gray (PAG) descending antinociceptive pathway is discussed.

Appetite stimulants have been used to help overcome decreased appetite and malnutrition in children and adults with various chronic illnesses, including cystic fibrosis (CF). Stimulants have included megestrol acetate (MA), cyproheptadine hydrochloride (CH), cannabinoids, hydrazine sulfate, anabolic hormones, and growth hormone. Many of these, including MA, have substantial side effects and may not be suitable for prolonged use. We previously studied the effects of CH on weight gain in a short-term (12 week) trial in CF with good results compared to placebo. Side effects were few, and weight gain was significant. In this study, we sought to determine the effects of CH over a longer term in order to assess its suitability for prolonged use. Sixteen CF children and adults enrolled in the original short-term study subsequently entered this study, and 12 completed the 9-month trial. All patients receiving placebo in the original short-term study received CH 4 mg up to four times a day in the long-term study continuation, and those receiving CH in the short-term study continued on the drug. No pill counts were done, and patients were queried at quarterly visits as to their CH use. Anthropometrics and spirometry were also done quarterly, and antibiotic use was quantified. Subjects who had changed from placebo (CH2 group) gained weight significantly over 3-6 months, and those continuing on CH (CH1 group) generally maintained previously gained weight over the duration of the study. Select spirometric measures improved in both groups but not significantly, and side effects were mild. CH appears to be an effective appetite stimulant in CF, and generally maintains its effect over time with an acceptable side-effect profile.

Cyproheptadine hydrochloride (C) shows an antihistaminic as well as antimuscarine, antiserotonic and sedative activity. The present work describes sensitive and reasonably selective poly(vinyl chloride) membrane electrodes for Cyproheptadine. They are based on the use of cyproheptadine-tetrakis(4-chlorophenyl)borate (C-TC1PB) and cyproheptadine-dipicrylamine (C-DPA) as a novel electroactive compound. Cyproheptadine ion-selective poly(vinyl chloride) membrane electrodes contain an ion-pair complex of Cyproheptadine with 2-nitrophenyloctyl ether (ENPO), 2-nitrodiphenyl ether (ENdP), bis(2-ethylhexyl)sebacate (DOS) and l-isopropyl-4-nitrobenzene (IPNB) as solvent mediators. The performance of the electrodes was investigated by measuring the e.m.f. values of 10 −2 –10 −7 mol 1 −1 Cyproheptadine hydrochloride. The effect of pH on the potential readings of the Cyproheptadine electrodes was checked by the recording on the e.m.f. of 10 −3 mol 1 −1 Cyproheptadine hydrochloride with pH values from 2.5 to 7.0. Potentiometric selectivity coefficient were measured by the separate solution method using a 10 −3 mol 1 −1 concentration of Cyproheptadine and the some concentration of interferent cations. The electrode obtained with C-TC1PB with DOS and electrode with C-DPA with IpNB were used in the potentiometric determination of Cyproheptadine in bulk substance and tablets PERITOL 4 mg as indicator electrodes. The results are in good agreement with those obtained by UV spectrophotometric method. Keywords: Cyproheptadine hydrochloride; Ion-selective electrode; Potentiometric titration; Cyproheptadine determination; Drag analysis

The British Pharmacopoeia (BP) monograph for cyproheptadine HCl tablets requires a ‘Related substances’ thin-layer chromatography (TLC) test. This test revealed an extraneous spot with an R f of 0.1 in certain cyproheptadine HCl tablets that were under ambient retention conditions as well as those on stability programs. An investigation utilizing LC-MS, direct infusion MS, NMR, and organic synthesis has identified that the spot results from the N -oxide of cyproheptadine (a genuine degradate) and a co-eluting cyproheptadine–dichloromethane adduct, an artifact formed during the sample extraction step in which dichloromethane is used in the extracting solvent.

We studied inflammatory reactions induced by dermal application of the beta-blocker propranolol (PRL) in ethanol to guinea pigs in order to elucidate the relation of the reactions with the cumulative PRL permeating amount through the stratum corneum or the PRL content in the stripped skin, and to investigate the chemical mediators responsible for the reactions. The cumulative PRL permeating amount through the stratum corneum increased rapidly up to 2 h after dermal application, then increased linearly with time up to 24 h after application. Visual observation revealed formation of erythema and edema at the applied site of PRL, and histopathological examination revealed infiltration of pseudoeosinophiles of dermis and epidermis and degeneration/necrosis of epidermis. In general, it was considered that the duration and the extent of these reactions were dependent on the PRL dosage and application time. It was expected that the cumulative PRL permeating amount through the stratum corneum could be used to predict possible inflammatory reactions during development of transdermal drug delivery systems. On the other hand, contact of PRL with guinea pig skin tissues released histamine, and intradermal injection of PRL caused an increase of capillary permeability at the site of application. Also, the inhibitory effects of anti-inflammatory agents (diphenhydramine, dexamethasone, indomethacin, cyproheptadine hydrochloride, CV3988 and AA-861) to PRL-induced erythema formation demonstrated that histamine and prostaglandins were responsible for the inflammatory reactions induced by PRL.

1. Metabolites formed during incubation of the antihistamine cyproheptadine hydrochloride with the zygomycete fungus Cunninghamella elegans in liquid culture were determined. The metabolites were isolated by hple and identified by mass spectrometric and proton nmr spectroscopic analysis. Two C elegans strains, ATCC 9245 and ATCC 36112, were screened and both produced essentially identical metabolites. 2. Within 72 h cyproheptadine was extensively biotransformed to at least eight oxidative phase-I metabolites primarily via aromatic hydroxylation metabolic pathways. Cyproheptadine was biotransformed predominantly to 2-hydroxycyproheptadine. Other metabolites identified were 1- and 3-hydroxycyproheptadine, cyproheptadine 10,11-epoxide, N-desmethylcyproheptadine, N-desmethyl-2-hydroxycyproheptadine, cyproheptadine N-oxide, and 2-hydroxycyproheptadine N-oxide. Although a minor fungal metabolite, cyproheptadine 10,11-epoxide represents the first stable epoxide isolated from the microbial biotransformation of drugs. 3. The enzymatic mechanism for the formation of the major fungal metabolite, 2-hydroxycyproheptadine, was investigated. The oxygen atom was derived from molecular oxygen as determined from 18O-labelling experiments. The formation of 2-hydroxycyproheptadine was inhibited 35, 70 and 97% by cytochrome P450 inhibitors metyrapone, proadifen and 1-aminobenzotriazole respectively. Cytochrome P450 was detected in the microsomal fractions of C. elegans. In addition, 2-hydroxylase activity was found in cell-free extracts of C. elegans. This activity was inhibited by proadifen and CO, and was inducible by naphthalene. These results are consistent with the fungal epoxidation and hydroxylation reactions being catalysed by cytochrome P450 monooxygenases. 4. The effects of types of media on the biotransformation of cyproheptadine were investigated. It appears that the glucose level significantly affects the biotransformation rates of cyproheptadine; however it did not change the relative ratios between metabolites produced.

Cyproheptadine hydrochloride (CH) is rarely used to treat adult patients with migraine in Japan because it causes sleepiness. In this study, we investigated the preventive effect of CH in 12 patients who had failed to respond to conventional preventive treatments among 103 migraine patients treated at our hospital. These 12 subjects had all received unsuccessful migraine prophylaxis with lomerizine, valproic acid and topiramate, or had discontinued these treatments due to adverse reactions. Initially, the subjects were given 4 mg CH before sleeping. In those who experienced no clinically significant sleepiness following the treatment, the drug was orally administered at 4 mg after breakfast as well (8 mg per day in total). Drug efficacy was evaluated by examining the frequency of migraine at one month and three months after the start of treatment. The frequency of migraine was dramatically reduced in all patients within 7 to 10 days after starting treatment. The average frequency of migraine during the three-month period was 2.6 episodes per month, representing a significant (p

Importance We describe a case of serotonin syndrome secondary to clozapine withdrawal and concomitant use of citalopram hydrobromide, a phenomenon that has been rarely reported. Observations This is a case report of a 47-year-old woman admitted to an academic medical center intensive care unit with coma, hypersalivation, hyperreflexia, and stimulus-induced clonus. The patient received a diagnosis of serotonin syndrome attributed to abrupt clozapine withdrawal with concomitant use of citalopram. She improved only minimally with supportive treatment (intravenous fluids, benzodiazapines, and withdrawal of selective serotonin-reuptake inhibitor) and received cyproheptadine hydrochloride on her third day of symptoms. Four hours after she received the loading dose of cyproheptadine, she was alert and oriented and at her baseline mental status, although some clonus remained. Conclusions and Relevance Serotonin syndrome can result from the abrupt withdrawal of a 5-hydroxytryptamine receptor 2A antagonist from a treatment regimen that also includes a medication that increases serotonin availability.

A highly sensitive and simple spectrofluorimetric method was developed for the determination of cyproheptadine hydrochloride (CYP) in its pharmaceutical formulations. The proposed method is based on the investigation of the fluorescence spectral behaviour of CYP in a sodium dodecyl sulphate (SDS) micellar system. In aqueous solution, the fluorescence intensity of CYP was greatly enhanced (150 %) in the presence of SDS. The fluorescence intensity was measured at 410 nm after excitation at 280 nm. The fluorescence–concentration plot was rectilinear over the range 0.2–2.0 μg/mL, with lower detection limit of 0.06 μg/mL. The proposed method was successfully applied to the assay of commercial tablets as well as content uniformity testing. The application of the proposed method was extended to test the in-vitro drug release of CYP tablets, according to USP guidelines. The results were statistically compared with those obtained by official USP method and were found to be in good agreement.

The reaction between haematoxylin reagent and eight antihistaminic drugs (chlorpheniramine maleate, pheniramine maleate, cyproheptadine hydrochloride; astemizole, terfenadine, ranitidine hydrochloride, famotidine and cimitidine) was investigated and utilized as the basis for a new, simple and sensitive spectrophotometric procedure for their determinations. The procedure is based on the reaction of the methanolic solution of the anti-histaminic compounds with haematoxylin reagent in 3x10-3 M boric acid to give a reddish-violet colour (lmax 555 nm). The absorbance was linear with all compounds over the 5-200 µg/ml general concentration range of the final measured antihistamine base solution. A good correlation was found between log A (1%, 1 cm) and pka values for six of the studied drugs. The method can be applied successfully to the analysis of commercially available tablet formulations. No interference was observed due to additives which are commonly present in tablet formulations or coformulated compounds such as phenazone, phenazone salicylate, sodium salicylate paracetamol, propyphenazone and caffeine.