薄层紫外扫描法测定五味子醇甲在大鼠体内的代谢及脑内分布

五味子醇甲为五味子乙醇提取物中有效成分之一,具有明显中枢安定作用,本文用薄层紫外扫描方法测定醇甲在大鼠及小鼠体内的吸收、分布、排泄及脑内分布。 大鼠口服醇甲后,胃肠吸收快,静注后血药浓度呈开放二室模型。组织分布以肺浓度最高,其次为肝、心、脑、肾、肠、脾及肠最低。脑内分布以下丘脑、纹体、海马浓度最高,其次为低位脑干及间脑,大脑皮层和小脑浓度较低。静注后由尿排出量很少。醇甲自整体小鼠的消失快。结果表明醇甲自胃肠道吸收快而完全,代谢及排泄较快,组织分布广。各脑区药物浓度的差别可能与其中枢作用有关。     

莨菪碱衍生物与M胆碱受体相互作用的构效关系

本文研究了一系列东莨菪碱衍生物对³H-QNB与大鼠脑M受体特异结合的影响。并通过比较它们的IC₅₀(用结合实验),药物—受体相互作用的解离常数K_B(抗乙酰胆碱引起的回肠收缩)以及抗震颤和抗匹罗卡品引起小鼠流涎的ED₅₀,分析了它们的构效关系。结果表明,K_B值与IC₅₀有很好的相关性(r=0.977),其线性回归的斜率为1.047;IC₅₀与抗震颤作用的ED₅₀之间相关性差,而log IC₅₀/ED₅₀值与它们的分配系数(logP)相关好(r=0.971),10号化合物的分配系数最大,中枢作用的选择性也最强。抗流涎ED₅₀与IC₅₀的相关系数为0.827。     

用脉冲伏安法观察多巴胺D1D2受体拮抗剂对大鼠纹体中DOPAC...

Dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) was detected by differential normal pulse voltammetry (DNPV) in chloral hydrate anesthetized rat striatum. The effects of some dopamine D-1 and D-2 antagonists on DOPAC concentration were observed in order to demonstrate the role of presynaptic D-1 and D-2 receptors in the feedback of dopamine synthesis and metabolism. The results showed that the mixed antagonists haloperidol (0.5 mg/kg s.c.) and chlorpromazine (5 mg/kg s.c.), the selective D-1 antagonist SCH23390 (1 mg/kg s.c.), and the selective D-2 antagonist sulpiride (5 mg/kg s.c.) all increased DOPAC concentration significantly. The percentages of increase were 140%, 102%, 26% and 40% in comparison with basal DOPAC concentration (14 +/- 2 mumol/L), respectively. These results indicate that not only presynaptic D-2 receptor regulates DA synthesis and metabolism, but that the presynaptic D-1 receptor also takes part in this feedback mechanism.     

异戊塞平和克塞平对大鼠脑内各受体亲和力的比较及慢性给药后的受体下调作用

用放射配体受体结合法测定表明:克塞平对多巴胺D_1受体的亲和力较异戊塞平高近20倍。两药对其它各受体的亲和力差別不大。慢性给药后,异戊塞平和克塞平均能使大鼠脑皮层5-HT_2受体的密度显著下降,而亲和力变化不明显。这种下调5-HT_2受体的作用发生在给异戊塞平后1～2周之间,给克塞平后的2～3周之间。慢性给药3周,异戊塞平和克塞平均未使大鼠脑皮层的β受体密度及亲和力产生显著变化。     

MK801慢性处理引起皮层神经元3H-GABA释放的改变

Excitatory amino acids are involved in acute and chronic neurodegenerativediseases.Little is known about the potential consequences of chronic blockade of NMDA receptors (onesubtype of excitatory amino acid receptors).Receptor function measured as ³H-GABA release inculture media after pretreatment with MK801 was studied in rat cortical neurons in primary cultures.Cultured neurons were exposed to 1μmol·L^-1 MK801 for 4 days since the 14th day.Glutamate( 1 mmol·L^-1 )evoked ³H-GABA release was shown to be significantly increased(control0.2174‰±1.40‰; MK801 treatment 0.763%±0.192%).KCl 40 mmol·L^-1 stimulation showedno such effect.This result suggests that the NMDA receptor function of releasing neurotransmitterschanged after chronic treatment with noncompetitive antagonists.     

伏安法测定MK—801和五味子醇甲对DN／DOPAC的影响

用差示复位脉冲伏安法（DNPV）在体测定了大鼠纹状体细胞外液中DA／DOPAC含量在缺血和再灌期的动态变化，并观察了MK－801和五味子醇甲对DA／DOPAC变化的影响，结果表明缺血6分钟期间DA／DOPAC峰显著增高，再灌流后，峰高逐渐下降。（＋）MK－801和五味子醇甲均能显著抑制缺血后纹状体内DA的释放。     

异戊塞平和克塞平对大鼠脑内各受体亲和力的比较及慢性给药后的受体下调作用

用放射配体受体结合法测定表明:克塞平对多巴胺D₁受体的亲和力较异戊塞平高近20倍。两药对其它各受体的亲和力差別不大。慢性给药后,异戊塞平和克塞平均能使大鼠脑皮层5-HT₂受体的密度显著下降,而亲和力变化不明显。这种下调5-HT₂受体的作用发生在给异戊塞平后1～2周之间,给克塞平后的2～3周之间。慢性给药3周,异戊塞平和克塞平均未使大鼠脑皮层的β受体密度及亲和力产生显著变化。     

薄层紫外扫描法测定五味子醇甲在大鼠体内的代谢及脑内分布

五味子醇甲为五味子乙醇提取物中有效成分之一,具有明显中枢安定作用,本文用薄层紫外扫描方法测定醇甲在大鼠及小鼠体内的吸收、分布、排泄及脑内分布。大鼠口服醇甲后,胃肠吸收快,静注后血药浓度呈开放二室模型。组织分布以肺浓度最高,其次为肝、心、脑、肾、肠、脾及肠最低。脑内分布以下丘脑、纹体、海马浓度最高,其次为低位脑干及间脑,大脑皮层和小脑浓度较低。静注后由尿排出量很少。醇甲自整体小鼠的消失快。结果表明醇甲自胃肠道吸收快而完全,代谢及排泄较快,组织分布广。各脑区药物浓度的差别可能与其中枢作用有关。     

SOME PHARAMACOLOGICAL ACTIONS OF THE SPORES OF GANODERMA LUCIDUM 赤芝孢子粉 AND THE MYCELIUM OF GANODERMA CAPENSIC (LLOYD) TENG 薄树芝藩丝体 CULTIVATED BY SUBMERGED FERMENTATION*

Ganoderma has bccn consideretl to be valuable tonic and ingested as a panacea. The results of our investigations in mice indicate that the alcohol-water soluble preparations ot Ganoderma possess sed:itive and anti-choliner- gic properties, whereas its etber soluble pre- parations increase the detoxicating ability of the liver.     

五味子醇甲对中枢神经系统单胺类递质的

Schizandrol A (2',3',4',1",2",3"-hexamethoxy-6, 7-dimethyl-1,2,3,4-dibenzo-1,3-cyclooctadien-6-ol) is one of the effective components in the dried fruit of Schizandra chinensis Bail. Previous studies have found that schizandrol A exerts inhibitory effects on the central nervous system (CNS). For the purpose of elucidating the mechanism of inhibition, the concentrations of monoamine neurotransmitters and their metabolites in rat brain and the effects of schizandrol A on some receptors were determined by the ion-pairing reversed-phase liquid chromatography with electrochemical detection method and competitive binding assay. In the neurotransmitter studies, significant elevations of dopamine and its metabolite DOPAC (in striatum) and DA (in hypothalamus) were observed after i.p. administration of 50 mg/kg or 100 mg/kg of schizandrol A. But the receptor binding experiments showed that schizandrol A had no affinity for dopamine D1 and D2 receptors. Serotonin receptors and alpha 1-,alpha 2-adrenergic receptors, and it did not affect the binding of dopamine to dopamine D1 or D2 receptors. These results indicate that the inhibition exerted by schizandrol A on the CNS may be related to the dopamine system, and the increase of dopamine turnover has nothing to do with dopamine receptors. The concentrations of the norepinephrine metabolite MHPG and the serotonin metabolite 5-HIAA showed changes in rat striatum and hypothalamus after schizandrol A treatment, but norepinephrine and serotonin levels were unaffected.