马钱子的毒性研究进展

钱子有较明显的药效,在临床及民间多有应用,但因马钱子治疗剂量与中毒剂量较接近,其临床应用的毒副反应报道也多,限制了马钱子的广泛使用.马钱子在治疗各种疾病中疗效肯定,是具有较大开发潜力的中药.文章回顾和分析了近年来研究有毒中药马钱子的文献,总结并归纳马钱子在化学成分、毒理学、药代动力学、减毒增效方面的研究进展,为今后深入进行中药毒性,特别是马钱子的毒性研究提供相关的依据,并针对马钱子减毒增效的机制为马钱子的临床应用提供了合理性的建议.     

POSSIBLE PARTICIPATION OF NMDA AND GLYCINE RECEPTORS BUT NOT GABAA RECEPTORS IN ENFLURANE-INDUCED OPISTHOTONUS IN MICE

1. We previously reported that volatile anaesthetics produce incidences of a transient opisthotonus in mice, a sign of CNS stimulation. This study was performed to investigate mechanisms by which enflurane-induced opisthotonus (EIO) occurs. 2. The effects of pretreatment of N-methyl-d-aspartate (NMDA) antagonists dizocilpine (MK-801; DIZ) and ketamine (KET), GABA_A antagonists picrotoxin (PIC), pentylenetetrazol (PTZ) and glycine antagonist strychnine (STR) on the incidence of EIO were determined. Prior to exposure to 2.0% enflurane in air, male ddN mice were given intraperitoneal injections of 0.2 mL saline (control), 0.5–5.0 mg/kg DIZ, 20–80 mg/kg KET, 2.9 mg/kg PIC, 40.0 mg/kg PTZ and 0.75 mg/kg STR. After the injection, the behavioural state of the mice was observed for 20 min (the pre-enflurane period). During the exposure to enflurane the time for immobilization, that is, anaesthetic induction time (IT), and the incidence of EIO were measured. 3. Dizocilpine (1.0–5.0 mg/kg) and KET (80 mg/kg) significantly (P<0.01) reduced both the incidence of EIO and IT in a dose-dependent manner. During the pre-enflurane period DIZ produced incidences (5–40%) of transient seizures in a dose-dependent manner, while KET did not induce them at all. The two GABA_a antagonists had no detectable effect on the EIO. Strychnine significantly enhanced the EIO. These CNS stimulants resulted in a 3–10% incidence of transient seizure and/or opisthotonus during the pre-enflurane period, but there was no correlation between DIZ-induced seizure and EIO. 4. These results suggest that the EIO is mediated by the NMDA and the STR-sensitive glycine receptors, but not the GABA_A receptor. We speculate that DIZ acts on the NMDA-receptor and/or disrupts the balance between the inhibitory and the excitatory systems.     

Anticonvulsant effects of neurotropin

Department of Normal Physiology, N. I. Pirogov Odessa Medical Institute. Department of Normal Physiology, I. M. Sechenov First Moscow Medical Institute. Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathophysiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 1, pp. 49–52, January, 1991.     

Influence of aminophylline and strychnine on the protective activity of excitatory amino acid antagonists against maximal electroshock-induced convulsions in mice

Summary Aminophylline reversed the protective action of both, D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid (D-CPP-ene — a competitive NMDA antagonist) and valproate (used as a conventional antiepileptic drug for comparative purposes) against maximal electroshock-induced seizures. The respective ED₅₀ values of aminophylline were 55.7 and 98.4mg/kg i.p. However, aminophylline (up to 100mg/kg i.p.) did not influence the protective efficacy of 1-(4-aminophenyl)-4-methyl-7,8-methyl-enedioxy-5H-2, 3-benzodiazepine (GYKI 52466 — a non-NMDA antagonist). Strychnine affected the protection provided by D-CPP-ene, GYKI 52466, and valproate against maximal electroshock — the ED₅₀ values of strychnine for the reversal of the anticonvulsive effects of D-CPP-ene, GYKI 52466 or valproate were 0.082, 0.35 and 0.28mg/kg s.c., respectively.An involvement of strychnine sensitive glycinergic receptor-mediated events in the mechanism of the anticonvulsive activity of excitatory amino acid antagonists and valproate may be postulated. The ineffectiveness of aminophylline to reduce the anticonvulsive effects of GYKI 52466 may distinguish a new class of antiepileptic drugs offering an advantage over conventional antiepileptics in patients with epilepsy, requiring aminophylline for pulmonary reasons.     

Influence of picrotoxin and strychnine on the spectral sensitivity of the turtle ERG b- and d-waves: II. Light adaptation

The aim of the present work was to investigate the role of GABA and glycine, the two main inhibitory neurotransmitters in the retina, in the spectral sensitivity coding under conditions of light adaptation. To study this question, spectral sensitivity curves, based on the turtle ERG responses to stimuli of different wavelengths, were constructed. The spectral sensitivity curves, obtained before and during treatment with picrotoxin (PT), a GABA_A antagonist, or with strychnine (ST), a glycine antagonist, were compared. Both PT and ST increased the b- and d-wave absolute sensitivity in a wavelength-dependent manner. PT significantly changed the shape of the b- and d-wave spectral sensitivity curves and the latter lost their peaks. It is concluded that, under conditions of light adaptation, GABA and glycine took part in the formation of the b- and d-wave spectral sensitivity curves, that both of them exerted an effect on the gain and that, furthermore, GABA had a well pronounced effect on the tuning of the spectral sensitivity curves.     

Central control of upper airway resistance regulating respiratory airflow in mammals

This article reviews recent studies on the importance of glycine receptors for both the spontaneous and the reflex respiratory modulation of the laryngeal abductors and adductors. Our findings show that strychnine blockade of glycine receptors within the brainstem changes the eupneic three-phase respiratory pattern into two phases. This has major implications for glottal control: (i) the inspiratory glottic abduction and early expiratory adduction were both compromised--a finding mimicked by 5% hypoxia; (ii) closure of the glottis during defensive upper airway reflexes became intermittent and the reflex apnoea reversed to sustained inspiratory discharge. Based on these data, we predict that periods of prolonged hypoxia, such as those that occur during sleep apnoeas, will constrain inspiratory glottic abduction thereby impeding inhalation.     

Chemical and statistical considerations in the determination of partition coefficients of weakly ionizable drugs and poisons

Equations have been developed that relate the concentration (or a parameter directly proportional to concentration, such as optical absorbance) of a weakly ionizable solute in a water-immiscible phase, in equilibrium with an aqueous phase, to the pH of the aqueous phase, the partition coefficient of the unionized solute and the phase volume ratio. These relationships have been used in the design of experimental methods for determining partition coefficients, which require measurement of solute concentration in only one phase. Data obtained in this way permit ready recognition of deviations from assumptions made in the development of the model; these assumptions include insolubility of the ionized solute in the water-immiscible phase and lack of interaction between buffer components and solute. Conditions for optimal liquid—liquid extraction of weakly ionizable solutes are more easily recognized. With these techniques, the negative logarithm of the acid dissociation constant (pK′_a) and the logarithm of the octanol—water partition coefficient (log P) have been measured for warfarin (pK′_a = 5.15 ± 0.04; log P = 2.82 ± 0.06), strychnine (pK′_a = 8.29 ± 0.02; log P = 2.23 ± 0.04), phenol (pK′_a = 9.88 ± 0.02; log P = 1.75 ± 0.05), procaine (pK′_a = 8.11 ± 0.04; log P = 1.10 ± 0.08), and ephedrine (pK′_a = 9.92 ± 0.01; log P = 1.65 ± 0.04) at 21°C.     

痹祺胶囊治疗类风湿性关节炎的药效研究及网络机制预测

目的 基于Ⅱ型胶原诱导的类风湿性关节炎（rheumatoid arthritis,RA）大鼠模型和网络药理学方法探讨痹祺胶囊的药效作用及作用机制。方法 SD大鼠采用Ⅱ型胶原蛋白造模,造模成功大鼠随机分为模型组,痹祺胶囊（0.05、0.10、0.20、0.40 g/kg）组及泼尼松（10 mg/kg）组和雷公藤总苷（10 mg/kg）组,连续给药15 d。持续监测大鼠体质量、足趾肿胀度和关节炎评分,苏木素-伊红染色考察大鼠踝关节病理变化,ELISA法测定血清细胞因子含量,初步评价痹祺胶囊治疗效果。选择痹祺胶囊中39个化合物为研究对象,依据反向药效团匹配方法和TCMSP、Uniprot等数据库预测化合物作用靶点,与通过OMIM、Dis Ge Net等数据库收集的RA相关靶点相互交互,将交互靶点借助Omicsbean、STRING等数据库平台对获得靶点进行基因本体功能和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析,利用Cytoscape软件构建“药材-化合物-靶点-通路-功效-疾病”网络,预测其可能的作用机制...     

薄层扫描法测定金龙祛痹丸中士的宁的含量

目的：马钱子粉系金龙祛痹丸中具毒怀的中药,为确保本品的安全有效,须建立其含量测定方法。方法：采用薄层扫描法测定金龙祛痹丸中士的宁的含量。以甲苯－丙酮－乙醇－浓氨试液为展开剂;单波长反射法锯齿扫描,测定波长为２５４ｎｍ。结果：通过方法学考察,点样量在０．５３５－３．２１０μｇ范围内线性关系良好,平均回收率为９９．１％。结论：试验表明,方法可靠,数据准确,操作简便、 行。