Search

Diffuse leptomeningeal glioneuronal tumor with the first symptom of acute rapid blindness in both eyes are rare in adolescents. We present a case of an adolescent female without a history of cancer who developed a dramatic loss of vision and eventually blindness, and was diagnosed as diffuse leptomeningeal glioneuronal tumor by cerebrospinal fluid cytology and enhanced MRI. In order to save vision, under the condition of ineffective dehydration treatment, timely emergency surgery to implant Ommaya sac drainage cerebrospinal fluid. According to the pathophysiological mechanism of cerebral edema, we added Edaravone to scavenge oxygen free radicals, Alprostadil to improve microcirculation, Monosialotetrahexosylganglioside nutrient nerve, Butylphthalide to promote collateral circulation, combined with hyperbaric oxygen and acupoint injection of Anisodine. Finally, the patient's vision returned to normal. Conclusion: when dehydration treatment is ineffective, timely surgery to reduce intracranial pressure, combined with comprehensive treatment, can effectively save vision.

Current study systematically investigated the interaction of two alkaloids, anisodine and monocrotaline, with organic cation transporter OCT1, 2, 3, MATE1 and MATE2-K by using in vitro stably transfected HEK293 cells. Both anisodine and monocrotaline inhibited the OCTs and MATE transporters. The lowest IC50 was 12.9 µmol·L-1 of anisodine on OCT1 and the highest was 1.8 mmol·L-1 of monocrotaline on OCT2. Anisodine was a substrate of OCT2 (Km = 13.3 ± 2.6 µmol·L-1 and Vmax = 286.8 ± 53.6 pmol/mg protein/min). Monocrotaline was determined to be a substrate of both OCT1 (Km = 109.1 ± 17.8 µmol·L-1, Vmax = 576.5 ± 87.5 pmol/mg protein/min) and OCT2 (Km = 64.7 ± 14.8 µmol·L-1, Vmax = 180.7 ± 22.0 pmol/mg protein/min), other than OCT3 and MATE transporters. The results indicated that OCT2 may be important for renal elimination of anisodine and OCT1 was responsible for monocrotaline uptake into liver. However neither MATE1 nor MATE2-K could facilitate transcellular transport of anisodine and monocrotaline. Accumulation of these drugs in the organs with high OCT1 expression (liver) and OCT2 expression (kidney) may be expected.

In this study, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) based on a broad-spectrum monoclonal antibody for tropane alkaloids (TAs) was established for the rapid screening of atropine, scopolamine, homatropine, apoatropine, anisodamine, anisodine and L-hyoscyamine residues in pig urine, pork and cereal flour samples through a simple sample preparation procedure. The half inhibitory concentrations of atropine, homatropine, L-hyoscyamine, apoatropine, scopolamine, anisodamine and anisodine were 0.05, 0.07, 0.14, 0.14, 0.24, 5.30 and 10.15 ng mL−1, respectivelyThe detection and quantitative limits of this method for TAs in samples were 0.18–73.18 and 0.44–74.77 μg kg−1. The spiked recoveries ranged from 69.88% to 147.93%, and the coefficient of variations were less than 14%. Good correlation (R2 = 0.9929) between the results of the ic-ELISA and the high performance liquid chromatography-tandem mass spectrometry support the reliability of the developed ic-ELISA method.

Background Chronic cerebral hypoperfusion is a common pathophysiological state in various cerebrovascular diseases. Anisodine has been reported to exert neuroprotective effects in cerebral ischemia/reperfusion (I/R) animal model. However, it is unclear whether anisodine hydrobromide, the hydrobromide format of anisodine, one of the tropic alkanes alkaloids, exhibits the same neuroprotective effect on chronic cerebral hypoperfusion(CCH) rats. Herein, we tried to unravel these issues. Methods CCH model in adult male Sprague-Dawley rats was established by permanent ligation of the bilateral common carotid arteries [two-vessel occlusion (2-VO)] surgery. Rats were randomly divided into six groups: sham, 2-VO, 2-VO + Butyl phthalide and sodium chloride injection (NBP, as positive control group), 2-VO + anisodine hydrobromide (AH)1.2mg/kg, 2-VO +AH0.6mg/kg, 2-VO +AH0.3mg/kg. Cognitive behavior was examined by Morris Water Maze Test. Neuronal survival and apoptosis were evaluated by Nissl staining and Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL staining). The relative monoamine neurotransmitter (5-hydroxytryptamine (5-HT), norepinephrine (NA)), the content of Ach, the activity of acetylcholin esterase (AchE) were measured in cholinergic system, and the protein expressions of Bcl-2, Bax, p-Akt and p-GSK-3βwere detected by Western blot assay. Results The results showed that there is significant memory impairment and a remarkable neuron necrosis and apoptosis, along with the dysfunction of the neurotransmitter systems and central cholinergic system in CCH rats. AH treatment could significantly improve cognitive deficits, while reducing neuron necrosis and apoptosis, apart from increasing the content of 5-HT and decreasing the activity of AchE markedly. Further study revealed that AH could promote the protein expression of Bcl-2, phosphorylation of Akt and GSK-3β, and downregulate the protein of Bax. Conclusion AH was demonstrated to ameliorate memory deficits by revising the imbalance of the monoamine neurotransmitter and cholinergic dysfunction. Moreover, AH can attenuate neuronal cell death and apoptosis by activating the Akt/GSK-3βsignaling pathway.

The aim of the present study was to observe the clinical efficacy and safety of recombinant tissue plasminogen activator (rt-PA) combined with compound anisodine in treating central retinal artery occlusion (CRAO). Forty-eight patients diagnosed with CRAO were randomly divided into a treatment group (24 cases) and a control group (24 cases). For the control group, nitroglycerin, 654-2, methazolamide, puerarin and compound anisodine were used for the treatment, along with oxygen, massage and other conventional treatments. Besides conventional therapy, the treatment group was also given intravenous rt-PA thrombolysis. Visual acuity, fundus oculi, visual field changes were taken as indicators for efficacy evaluation. It was found that the total effective rate of the control group was 70.83%, while that for the treatment group was 91.67%, and the comparative difference between the two groups was of statistical significance (p

目的：应用复方樟柳碱(compound anisodine, CA)注射液行颞浅动脉旁注射治疗干眼症，探讨干眼恢复的效果。方法：采用复方樟柳碱注射液2 ml对单纯性干眼症患者50例和难治性干眼症患者82例，行颞浅动脉旁注射2~5个疗程，观察注射前后干眼的各项指标：泪膜破裂时间(break-up time, BUT)、基础泪液分泌试验(Schinmer II test, Sit II)、角膜荧光素钠染色(fluorescein, FL)及干涩、刺痛、流泪、畏光、异物感、视物模糊等症状。结果：治疗2~5个疗程后分别观察上述指标，干涩、异物感减轻，刺痛、流泪、畏光、视物模糊消失，与治疗前比较BUT明显延长(t = 25.366, 22.125, 17.148)，SIt分泌增加(t = −14.726, −17.213, −7.256)，FL染色率也明显减少。差异均有统计学意义(p < 0.01)。结论：无论是单纯性干眼症和难治性干眼症患者采用复方樟柳碱注射液行颞浅动脉旁注射治疗后症状和体征均有显著性改善。 Objective: To evaluate the improvement of xerophthalmia following acupoint injection compound anisodine (CA) in the patients with scheroma. Methods: This randomized study involved 50 cases (50 eyes) with simple patients with scheroma and 82 cases (82 eyes) with refractory patients with scheroma. All patients with scheroma were treated for 2 - 5 courses of treatment by acupoint in-jection compound anisodine 2 milliliter (ml) in lateral arteria temporalis superficialis. The symp-toms of dry eye, tear break-up time (BUT), Schinmer II test (SIt) value and corneal fluorescein staining (FL), including dry feeling, stinging sensation, lachrymation, photophobia, fricative feeling, indistinct vision were measured pre-therapy and post-treatment. Results: At post-treatment for 2 - 5 courses, all symptoms of aforementioned disappeared. The subjective complains of dry eye improved. The mean SIt (t = −14.726, −17.213, −7.256) and BUT (t = 25.366, 22.125, 17.148) lengthened significantly (p < 0.01 for normal group). The FL scores decreased significantly. There were statistically significant differences (p < 0.01). Conclusions: Acupoint injection compound an-isodine in lateral arteria temporalis superficialis can improve the symptoms and signs of simple and refractory patients with scheroma.

A Ru(bpy)32+-based electrochemiluminescence method coupled with capillary electrophoresis has been developed for the separation and detection of two tropane alkaloids, anisodamine and anisodine, within 7 min with a platinum microelectrode modified with a europium(III)-doped Prussian blue analog film as the working electrode. Under optimized conditions, the ECL intensity was in proportion to the log values of anisodine and anisodamine concentrations in the range 5.0 × 10−6–1.0 × 10−3 mol L−1 (r = 0.9992) for anisodine and 1.0 × 10−6–1.0 × 10−3 mol L−1 (r = 0.9991) for anisodamine, with detection limits of 1.2 × 10−7 mol L−1 for anisodine and 4.3 × 10−8 mol L−1 for anisodamine. The proposed method has been applied to identify and detect the two alkaloids in the different parts (seeds, roots and leaves) of Anisodus tanguticus. The results showed that anisodine existed in all samples, including the seeds, roots and leaves of the plant, and its content was highest in the seeds and lowest in the leaves. However, anisodamine was not found in the samples mentioned above due to the low levels in the plant and maybe the interreaction between anisodamine and other chemicals in the plant. Finally, average recoveries of 98.0–107.0% were obtained.

Background: Compound anisodine (CA) is a compound preparation made from hydrobromide anisodine and procaine hydrochloride. The former is an M-choline receptor blocker with the function of regulating the vegetative nervous system, improving microcirculation, and so on. The latter is an antioxidant with the activities of neuroprotection. This study aimed to investigate the potential neuroprotection of CA, which affects the degeneration of the retinal ganglion cells (RGCs) in an animal model with chronic ocular hypertension. Methods: Female C57BL/6J mice (n = 24) were divided randomly into four groups: Normal control group without any treatment (Group A, n = 6); CA control group with feeding the CA solution (Group B, n = 6); microbeads (MBs) control group with injecting MB into the anterior chamber (Group C, n = 6); CA study group with MB injection and with feeding the CA solution (Group D, n = 6). Intraocular pressure (IOP) was measured every 3 days after MB injection. At the 21st day, neurons were retrograde-labeled by Fluoro-Gold (FG). Animals were sacrificed on the 27th day. Retinal flat mounts were stained immunohistologically by β-III-tubulin. FG-retrograde-labeled RGCs, β-III-tubulin-positive RGCs, and β-III-tubulin-positive nerve fibers were quantified. Results: Mice of Groups C and D expressed the incidence of consistent IOP elevation, which is above the IOP level of Group A with the normal one. There is no significant difference in IOP between Groups A and B (P > 0.05). On the 27th day, there were distinct loss in stained RGCs and nerve fibers from Groups C and D compared with Group A (all P < 0.001). The quantity was significantly higher in Group D as compared to Group C (all P < 0.001) but lower than Group A (all P < 0.001). There was no significant difference in the quantity of RGCs and nerve fibers between Groups A and B (all P > 0.05). Conclusions: These findings suggest that CA plays an importantly neuroprotective role on RGCs in a mouse model with chronic ocular hypertension.

Purpose : To investigate the spectrum-effect relationships between high performance liquid chromatography with photodiode array detection (HPLC-DAD) fingerprint and analgesic activity of Anisodus tanguticus (Maxim.) Pascher (Solanaceae) (AT) roots. Methods : Analgesic activity of AT roots was evaluated by acetic acid-induced writhing test in mice. Fingerprint of AT roots was established by HPLC-DAD. After oral administration of AT roots extract, intra-gastric contents of caffeoylputrescine, anisodine, fabiatrin, scopolin, scopolamine, anisodamine and atropine in mice were determined by HPLC-DAD. Spectrum-effect relationships between HPLCDAD fingerprint and analgesic activity were investigated using bivariate correlation analysis. Results : Following treatment with different batches of AT roots extract, acetic acid-induced writhing responses in mice were inhibited significantly (p < 0.05 or 0.01), with inhibitions of 26.62 - 55.13 %, relative to the control group. Sixteen common peaks were obtained by fingerprint analysis. Peaks 1, 2, 6, 7, 8, 9 and 12 were identified as caffeoylputrescine, anisodine, fabiatrin, scopolin, scopolamine, anisodamine and atropine, respectively. Bivariate correlation analysis between analgesic activity of AT roots and 16 common peaks areas indicated the contributions of 16 common peaks to analgesic activity of AT roots. Surprisingly, bivariate correlation analysis between analgesic activity of AT roots and intragastric contents of above-named 7 constituents revealed that the contributions of the 7 constituents to analgesic activity of AT roots were different from those based on their peak areas. Conclusion : This study provides scientific justification for the investigation of the active constituents of AT root with a view to its standardization. Keywords : Anisodus tanguticus root, Analgesic activity, HPLC-DAD fingerprint, Bivariate correlation analysis

© Georg Thieme Verlag KG Stuttgart New York. Four new hydroxycinnamic acid amides, scotanamines A-D (1-4), and seven known alkaloids, including N 1,N 10-di-dihydrocaffeoylspermidine (5), scopolamine (6), anisodamine (7), hyoscyamine (8), anisodine (9), caffeoylputrescine (10), and N 1-caffeoyl-N 3-dihydrocaffeoylspermidine (11), were obtained from the roots of Scopolia tangutica. The present study represents the first recognition of hydroxycinnamic acid amides containing putrescine or spermidine in S. tangutica. Compound 1, in particular, contains a moiety resulting from the condensation of nortropinone and putrescine. Compound 2 exhibited moderate agonist activity at the μ-opioid receptor (EC50=7.3μM). Compound 2 was tested in vivo and induced analgesia in mice. The analgesic effect was recorded using the tail-flick assay and was reversed by naloxone.

The compound series of traditional anticholinergics [atropine (Atr), anisodamine (Ani), anisodine (AT3), and scopolamine (Sco)], naturally occurring belladonna alkaloid, have been approved for numerous therapeutic uses since 1970s. Tiotropium, a novel M receptor antagonist for the treatment of chronic obstructive pulmonary disease, was structurally modified based on atropine-like drugs. Clinical phenomena suggested that the changes of substituent group were related to the pharmacokinetic and pharmacodynamic characteristics of the agents. In an attempt to compare the pharmacokinetics of the series of anticholinergics and investigate the subsets motivating selective anticholinergic potencies, a sensitive LC–MS/MS method was established to analyze the differences of pharmacokinetic parameters. In this paper, we determined the pharmacokinetics of atropine, anisodamine, anisodine, scopolamine, and tiotropium after i.v. and i.g. single dose administration. After i.v. administration, the maximum drug plasma concentrations (C max) of Atr, Ani, AT3, and Sco were 274.25 ± 53.66, 267.50 ± 33.16, 340.50 ± 44.52, and 483.75 ± 78.13 ng/mL. Tiotropium had a slightly higher area under the curve with a significant increase of C max value. Because of their partial solubility, Atr, Ani, AT3, and Sco had different bioavailability in rats of 21.62, 10.78, 80.45 and 2.52 %, respectively. Following i.g. administration of tiotropium, the C max value below 20 ng/mL revealed the very low oral absorption. The urinary excretion rates of Atr, Ani, AT3, Sco and tiotropium were 11.33, 54.86, 32.67, 8.69 and 73.91 %. This work provided relatively comprehensive preclinical data on the series of anticholinergics, which may be used to explain the clinical adverse effects and applications.

Tropane alkaloids (TAs) including hyoscyamine, anisodamine, anisodine and scopolamine are widely used as anticholinergic agents, which act on the parasympathetic nervous system, and their clinical demands are increasing rapidly. Anisodus acutangulus is a solanaceous perennial plant that is endemic to China with good potential for TA production and classified as an endangered species in China. Therefore there is a need to improve the TA production in this resource plant by biology methods. In our research, three different important elicitors including methyl jasmonate (MJ), yeast elicitor (YE) and abscisic acid (ABA) were used to study their effects on TA production, and genes expressions in A. acutangulus plant under each treatment were examined. The results revealed that TA production was induced by all the three treatments. However, its quantity varies with inducers used. The effect induced by MJ and YE were significant, while the effect induced by ABA was not obviously. To our knowledge, this is the first report on the relationship between TA production and genes expression profile induced by different elicitors in cultivated A. acutangulus plant, which should provide some useful information on how to improve TA production with the cultivated A. acutangulus plant in the near future.

Based on an Eu-PB modified platinum electrode as the working electrode, a method for the simultaneous determination of the four tropane alkaloids, anisodamine, scopolamine, atropine and anisodine, by capillary electrophoresis with electrochemiluminescence detection (CE-ECL) has been established. The effects of several factors, such as the detection potential, the acidity and concentration of the running buffer, and the content of the methanol additive were investigated for the improvement of separation ability and detection sensitivity. Under the optimized conditions, these four components could be fully separated from each other in a 20 mmol/L phosphate (pH 8.0) containing 7% (v/v) methanol buffer within 6 min. The relative standard deviations of the peak area and migration time were less than 5.0% and 1.1% (n = 12) respectively for all the four compounds. Thus, the method has been successfully applied to the determination of anisodamine, scopolamine in Przewalskia tangutica Maxim. The average amounts of 27.8 g/kg anisodamine and 4.43 g/kg scopolamine were found in the herbal root-stalk sample. The recoveries of the tropane alkaloids were 97.8% - 102%.

Anisodine (l-6,7-epoxy-3-tropyl-alpha-hydroxytropate), which was isolated from the medicinal plant Scopolia tanguticus Maxim, was the first efficiently prepared using 6-beta-acetyltropine as the starting material via a key step of the Sharpless asymmetric dihydroxylation (AD). The intermediate compounds 10 and 11 showed promising cholinergic activity.

A simple and rapid high-performance liquid chromatographic-electrospray ionization (ESI) tandem mass spectrometric method has been developed for elucidation of the structures of the metabolites of anisodine in rat urine after administration of a single dose (20 mg). Different extraction techniques (free fraction, acid hydrolysis, and enzyme hydrolysis) were compared for investigation of the metabolism of anisodine. After extraction the pretreated samples were injected into a reversed-phase C18 column with 60:40 (v/v) methanol–0.01% triethylamine solution (2 mM, adjusted to pH 3.5 with formic acid) as mobile phase. Detection was by on-line MS-MS. Identification of the metabolites and elucidation of their structure were performed by comparing changes in molecular masses (ΔM), retention-times, and spectral patterns of product ions with those of the parent drug. At least twenty metabolites (norscopine, scopine, α-hydroxytropic acid, aponoranisodine, apoanisodine, noranisodine, anisodine N-oxide, hydroxyanisodine, hydroxyanisodine N-oxide, methoxyanisodine, hydroxymethoxyanisodine, trihydroxyanisodine, dihydroxymethoxyanisodine, hydroxydimethoxyanisodine, glucuronide conjugates, and sulfate conjugates of noranisodine, hydroxyanisodine and the parent drug) and the parent drug were found in the urine after ingestion of 20 mg anisodine by healthy rats. Anisodine N-oxide, hydroxyanisodine, and the parent drug were detected in rat urine for up 120 h after ingestion of the drug.

Tropane alkaloids (TA) are bioactive small molecules containing an esterified bicyclic tropane moiety. TA represent natural plant poisons and (semi)synthetic drugs, most of them (e.g. atropine, benzatropine, N-butyl scopolamine, cimetropium, homatropine, ipratropium, N-methyl scopolamine, scopolamine, tiotropium, trospium) antagonizing acetylcholine at muscarinic receptors (MR) and some of them (e.g. bemesetron, granisetron, scopolamine, tropisetron) antagonizing serotonin at the 5-HT3 receptor (5-HT3R). Therapeutic effects on MR include mydriasis, spasmolysis of the gastrointestinal tract, overactive bladder and of the respiratory system. Due to their binding to the 5-HT3R, TA are used as antiemetic to treat vomiting and nausea. In addition, a few TA interact with α1-adrenoreceptors thus being used to improve blood flow for the treatment of septic shock (e.g. anisodamine, anisodine). Furthermore, ingestion of plants containing natural TA such as hyoscyamine and scopolamine may cause fatal intoxications.

Background Tropane alkaloids (TA) including anisodamine, anisodine, hyoscyamine and scopolamine are a group of important anticholinergic drugs with rapidly increasing market demand, so it is significant to improve TA production by biotechnological approaches. Putrescine N-methyltransferase (PMT) was considered as the first rate-limiting upstream enzyme while tropinone reductase I (TRI) was an important branch-controlling enzyme involved in TA biosynthesis. However, there is no report on simultaneous introduction of PMT and TRI genes into any TA-producing plant including Anisodus acutangulus (A. acutangulus), which is a Solanaceous perennial plant that is endemic to China and is an attractive resource plant for production of TA. Results In this study, 21 AaPMT and AaTRI double gene transformed lines (PT lines), 9 AaPMT single gene transformed lines (P lines) and 5 AaTRI single gene transformed lines (T lines) were generated. RT-PCR and real-time fluorescence quantitative analysis results revealed that total AaPMT (AaPMT T) and total AaTRI (AaTRI T) gene transcripts in transgenic PT, P and T lines showed higher expression levels than native AaPMT (AaPMT E) and AaTRI (AaTRI E) gene transcripts. As compared to the control and single gene transformed lines (P or T lines), PT transgenic hairy root lines produced significantly higher levels of TA. The highest yield of TA was detected as 8.104 mg/g dw in line PT18, which was 8.66, 4.04, and 3.11-times higher than those of the control (0.935 mg/g dw), P3 (highest in P lines, 2.004 mg/g dw) and T12 (highest in T lines, 2.604 mg/g dw), respectively. All the tested samples were found to possess strong radical scavenging capacity, which were similar to control. Conclusion In the present study, the co-expression of AaPMT and AaTRI genes in A. acutangulus hairy roots significantly improved the yields of TA and showed higher antioxidant activity than control because of higher total TA content, which is the first report on simultaneous introduction of PMT and TRI genes into TA-producing plant by biotechnological approaches.

Ion-pair high-performance liquid chromatography was combined with column switching to determine tropane alkaloids, mainly hyoscyamine, in complex preparations of gastrointestinal drugs using a three-pump system. The mobile phases were all the same except for the concentration of the counter ion, sodium dodecyl sulphate (SDS). The tropane alkaloid fraction immediately eluted by the primary mobile phase without SDS from a pretreatment column was transferred to an analytical column and separated by the ion-pair mobile phase. A tertiary pump was used to supply SDS to the trapped fraction in the loop after elution through the pretreatment column. Linear calibration graphs were obtained in the range 0.3–30 μg/ml for anisodine, anisodamine and scopolamine and 0.3–300 μ/ml for hyoscyamine (atropine). Hyoscyamine levels in model preparations of gastrointestinal drugs were determined by this column switching system with a recovery of about 97%.

Tropane alkaloids (TA) including hyoscyamine, anisodamine, scopolamine and anisodine, are used medicinally as anticholinergic agents with increasing market demand, so it is very important to improve TA production by metabolic engineering strategy. Here, we report the simultaneous introduction of genes encoding the branch-controlling enzyme tropinone reductase I (TRI, EU424321) and the downstream rate-limiting enzyme hyoscyamine-6β-hydroxylase (H6H, EF187826) involved in TA biosynthesis into Anisodus acutangulus hairy roots by Agrobacterium-mediated gene transfer technology. Transgenic hairy root lines expressing both TRI and H6H (TH lines) produced significantly higher (P0.05) levels of TA compared with the control and single gene transformed lines (T or H lines). The best double gene transformed line (TH53) produced 4.293 mg g(-1) TA, which was about 4.49-fold higher than that of the control lines (0.96 mg g(-1)). As far as it is known, this is the first report on simultaneous introduction of TRI and H6H genes into TA-producing plant by biotechnological approaches. Besides, the content of anisodine was also greatly improved in A. acutangulus by over-expression of AaTRI and AaH6H genes. The average content of anisodine in TH lines was 0.984 mg g(-1) dw, about 18.57-fold of BC lines (0.053 mg g(-1) dw). This is the first time that this phenomenon has been found in TA-producing plants.

The inclusion complexations of β-cyclodextrin with four hyosoyamine drugs were investigated by using miorocalorimetry. The drugs studied are anisodamine, scopolamine, anisodine and atropine. Our microcalorimetric results demonstrated that all the inclusion complexes were found to be 1:1 and their thermodynamio parameters of formation constants K, △G°, △H° and △S° were obtained. The complexations are predominantly due to favorable enthalpy changes and unfavorable entropy changes. This indicates that hydrophobia interaction is not predominant. The effects concerning with steric hindrance and chirality were also discussed. The ~1H NMR speotra strongly suggested that the drug molecule was included into the hydrophobic cavity of β-cyolodextrin.

The cholinoceptor antagonists anisodamine and anisodine are widely used in the People's Republic of China for the management of acute circulatory shock but the mechanism of their beneficial effects is not fully known; we therefore investigated if these agents possessed adrenoceptor blocking properties. The antagonistic effect of anisodamine and anisodine against the specific binding of the alpha 1-adrenoceptor ligand [3H]-WB-4101 to cardiac and brain tissue membrane preparations and against the effects of phenylephrine on isolated aortic strips and left atria of rats were compared with classical muscarinic receptor and adrenoceptor blocking agents. Both anisodamine and anisodine possessed alpha 1-adrenoceptor blocking properties; the order of potency of various agents in displacing the binding of [3H]-WB-4101 to receptors and in antagonizing the effects of phenylephrine on aortic strips and left atria was: prazosin greater than atropine greater than anisodamine greater than scopolamine greater than anisodine. It is concluded that both anisodamine and to a lesser extent anisodine possess alpha 1-adrenoceptor blocking properties; this antagonistic activity of anisodamine may contribute to its salutary effects on the microcirculation. However, it is unlikely that anisodine produces a significant adrenoceptor blockade in the clinically used dose-range.