Janbroers J M
Clin Ther. 1984;6(4):434-50.
Pinazepam, a benzodiazepine derivative, differs from other drugs of its class by the presence of an unsaturated bond, the propargyl group, at the N-1 position. Its toxicity is less than that of diazepam. In animals, pinazepam controls anxiety and aggressiveness. This effect seems to be associated with a particularly low hypnotic effect and with a limited impairment of motor coordination. Pinazepam shows less cortical activity at the anxiolytic level than does diazepam on EEG. The drug's mechanism of action primarily involves modification in the region of the limbic system. Extensive pharmacokinetic studies have demonstrated rapid gastrointestinal absorption of pinazepam. The metabolic pathway is N-1 dealkylation and C-3 hydroxylation. In dogs, pinazepam reaches the steady state in one day and its main metabolite, depropargylpinazepam (N-desmethyldiazepam) in six days, thus achieving a much higher blood concentration than the parent drug. In rabbits, a first-pass effect is evident. Both compounds are converted to oxazepam, which is pharmacologically inactive and is eliminated in the urine. Pinazepam and depropargylpinazepam cross the placenta and appear in human milk. In dogs, accumulation could not be demonstrated at the end of treatment with 10 mg of pinazepam for 20 days. All the findings in animals were confirmed in humans. In clinical trials with open or controlled design, pinazepam, compared with diazepam, showed a significant and purely anxiolytic action in patients suffering from anxiety with or without somatic manifestations, particularly in gastrointestinal disorders. Even though it is not a specific hypnotic drug, it seems to help patients in whom the physiological course of the sleep is disturbed. The standard dosage is 10 mg daily, divided in two doses. Pinazepam is well tolerated in humans. About 5% of patients experience mild sedation. Other side effects are infrequent and minor. In the studies there was no evidence of impairment of motor coordination or of intellectual performance. There were no reports of a rebound phenomenon or drug dependence. These findings indicate that pinazepam is a pure anxiolytic agent devoid of hypnotic effect or motor disorders, characteristics that make it a useful drug for daytime use.
匹那西泮是一种苯二氮䓬衍生物，因其在N-1位存在不饱和键（炔丙基）而与该类其他药物不同。其毒性低于地西泮。在动物实验中，匹那西泮可控制焦虑和攻击性。这种作用似乎与特别低的催眠作用以及对运动协调的有限损害有关。在脑电图上，匹那西泮在抗焦虑水平时的皮层活动比地西泮少。该药物的作用机制主要涉及边缘系统区域的改变。广泛的药代动力学研究表明匹那西泮在胃肠道吸收迅速。代谢途径为N-1去烷基化和C-3羟基化。在犬类中，匹那西泮一天内达到稳态，其主要代谢产物去炔丙基匹那西泮（N-去甲基地西泮）在六天内达到稳态，因此其血药浓度比母体药物高得多。在兔类中，首过效应明显。两种化合物均转化为奥沙西泮，奥沙西泮无药理活性，经尿液排出。匹那西泮和去炔丙基匹那西泮可穿过胎盘并出现在人乳中。在犬类中，用10毫克匹那西泮治疗20天结束时未发现蓄积现象。在人体中证实了动物实验的所有结果。在开放或对照设计的临床试验中，与地西泮相比，匹那西泮对伴有或不伴有躯体表现的焦虑患者，尤其是胃肠道疾病患者，显示出显著且纯粹的抗焦虑作用。尽管它不是一种特定的催眠药物，但似乎对睡眠生理过程受到干扰的患者有帮助。标准剂量为每日10毫克，分两次服用。匹那西泮在人体中耐受性良好。约5%的患者会出现轻度镇静。其他副作用很少且轻微。在研究中，没有证据表明运动协调或智力表现受到损害。也没有关于反跳现象或药物依赖的报道。这些发现表明匹那西泮是一种纯粹的抗焦虑药物，没有催眠作用或运动障碍，这些特性使其成为白天使用的有用药物。
