包甲素合成类似物的过筛试验

本文采用豚鼠离体纵长肌累积剂量-效应曲线法,求解离常数(KD)及最大效应(Emax)值,以氨甲酰胆碱为标准药,对14个莨菪烷类化合物进行比较,结果表明:6β-乙酰氧基去甲莨菪烷,3α-对甲苯甲酰氧基-6β-乙酰氧基莨菪烷及3α,6β-二乙酰氧基莨菪烷三化合物有明显的M受体激动作用。其构-效关系提示:6β-乙酰氧基是M激动作用的关健结构,N位上的CH_3能削弱这一作用。     

Ipvelutine, 7β-Acetoxy-2α-(tigloyloxy)tropane,an Unusual Tropane Alkaloid from Ipomoea velutina R. Br. (Convolvulaceae)

Convolvulaceae provide a rich source of tropane alkaloids, however, 2-substituted tropanes have been described for only few species of this taxon. In this note, 2,7-diesters such as ipvelutine [7β-acetoxy-2α-(tigloyloxy)tropane] isolated from the vegetative parts of the Australian Ipomoea velutina R. BR. are described as a new group of tropane diesters.     

Dopamine transporter availability and depressive symptoms during alcohol withdrawal

Alcohol-related temporary depressive symptoms are hypothesized to be related to dopaminergic dysfunction. The aim of this study was to investigate whether or not depressive symptoms correlate with reduced dopamine transporter (DAT) availability. We studied the DAT availability in 28 alcoholic subjects with β-CIT ([123-iodium]-2-β-carbomethoxy-3-β-(4-iodophenyl)-tropane) single photon emission tomography (SPET) and found a reduction in DAT availability during withdrawal that subsequently showed a significant increase during sobriety. The relationship between DAT availability and Montgomery-Åsberg Depression Rating scale scores, both during withdrawal and after sobriety, was assessed. The main finding was a statistically significant correlation between DAT variances and depressive symptom scores during both states. The findings indicate a possible dopaminergic etiology for depressive symptoms in alcohol withdrawal, which suggests that dopaminergic antidepressants might be beneficial in the treatment of alcohol withdrawal.     

^99mTc-TRODAT-1脑SPECT显像对帕金森病的早期诊断价值

目的：评价脑^99Tc^m-2β[N，N’-双（2-巯乙基）乙撑二胺基]甲基，3β-（4-氯苯基）托烷（^99mTe—TRODAT-1）SPECT多巴胺转运蛋白（dopaminetransporter，DAT）显像对帕金森病（Parkinson’Sdisease，PD）早期诊断的临床应用价值。方法：对21例早期PD患者（Hoehn-Yahr1级12例，2级9例）及15例健康对照者分别进行”“Te-TRODAT-1SPECT脑显像，剂量为740MBq。应用计算机感兴趣区技术及2个数学模型分别计算早期PD患者及健康对照者双侧纹状体体积（V，cm^3）、质量（W，g），代表相应部位的多巴胺转运蛋白功能水平。结果：健康对照组SPECT扫描示DAT核素密度集中于双侧纹状体呈红色，左右基本对称，双侧纹状体貌似“熊猫眼”。早期PD患者双侧纹状体DAT核素分布不均匀，形状各异，其体积和质量均低于健康对照者，差异有显著性（P〈0.01）；早期PD患者症状对侧纹状体体积和质量均显著低于症状同侧（P〈0.01）；Hoehn—Yahr2级PD患者双侧纹状体DAT体积和质量均低于Hoehn—Yahr1级PD患者，差异有显著性（P〈0.05）。结论：DAT数量减少是PD发病的重要环节之-，^99mTc-TRODAT-1脑SPECT显像有勖于PD的早期临床诊断。     

Further evaluation of the reinforcing effects of the novel cocaine analog 2β-propanoyl-3β-(4-tolyl)-tropane (PTT) in rhesus monkeys

 2β-Propanoyl-3β-(4-tolyl)-tropane (PTT) is a cocaine analog which has been shown in rhesus monkeys to have cocaine-like discriminative stimulus effects and a long duration of action (>8 h), yet does not function as a reinforcer when substituted for cocaine in monkeys responding under a fixed-interval 5-min schedule (Nader et al. 1997). The purpose of the present study was to evaluate the reinforcing effects of PTT under a fixed-ratio (FR) schedule and to determine if decreasing the inter-injection interval would influence the reinforcing effects of PTT. Male rhesus monkeys (n=3) were trained to respond under a multiple FR 30 food-drug-food schedule. When responding was stable, cocaine (0.003–0.3 mg/kg per injection) or PTT (0.001–0.03 mg/kg per injection) was available during the drug component for at least five consecutive sessions and until stable responding was observed. To investigate whether the inter-injection interval would influence PTT-maintained response rates, the time-out (TO) following PTT injections was reduced from 180 or 300 s to 10 s for at least five consecutive sessions. Cocaine-maintained response rates were characterized as an inverted-U shaped function of dose, with peak rates maintained by 0.03 mg/kg per injection cocaine. PTT (0.001–0.03 mg/kg per injection) maintained response rates significantly higher than rates maintained by the PTT vehicle, but significantly lower than cocaine-maintained response rates; PTT intake increased with dose. A reduction of the TO following PTT injections to 10 s did not alter PTT-maintained response rates or total session intake. Self-administered PTT was more potent than cocaine at decreasing food-maintained responding. These results suggest that for long-acting compounds like PTT, reinforcing effects are more likely to be observed when the drug is available under a ratio-based schedule, compared to an interval-based schedule. Received: 3 May 1997 / Final version: 11 October 1997