Petkov V D, Lazarova M B, Belcheva S, Getova D, Petkova B, Petkov V V, Stancheva S, Alova L, Konstantinova E, Todorov I
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
Acta Physiol Pharmacol Bulg. 1991;17(2-3):61-74.
The original pyrrolidine derivatives with putative nootropic effect: para-chloro-phenoxyacetyl-2-pyrrolidinone (Mf-P), 1-adamantanyl-2-pyrrolidinone (A-P), 2-oxo-1-pyrrolidine-3,7-dimethylxanthine (A-T) and para-benzoyl-1,4-dipyrrolidinone (p-P), were studied. Toxicological screening performed on mice demonstrated the low toxicity of the compounds. Five- or seven-day oral administration of the substances to rats in a dose of 100 mg/kg weight facilitated the learning process and improved the memory of the rats with most of the conditioned-reflex methods used. Application of Mf-P to 2- and 24-month-old rats for 8 days induced changes in the levels of some biogenic monoamines in the brain structures studied. The results obtained, as well as the results of other studies in this laboratory, show that the pyrrolidine derivatives studied, which can be considered to be original new aniracetam analogues, improve the memory process. This effect varies strongly depending on the regime of application of the compounds studied, on the memory capacity of the experimental animals and on the experimental method used. The changes in the brain neurotransmission induced by the substances studied play an essential role in their mechanism of action.
对氯苯氧基乙酰基 - 2 - 吡咯烷酮(Mf - P)、1 - 金刚烷基 - 2 - 吡咯烷酮(A - P)、2 - 氧代 - 1 - 吡咯烷 - 3,7 - 二甲基黄嘌呤(A - T)和对苯甲酰基 - 1,4 - 二吡咯烷酮(p - P)进行了研究。对小鼠进行的毒理学筛查表明这些化合物毒性较低。以100mg/kg体重的剂量对大鼠进行为期五天或七天的口服给药,在使用的大多数条件反射方法中,促进了大鼠的学习过程并改善了其记忆。将Mf - P应用于2个月和24个月大的大鼠8天,诱导了所研究脑结构中一些生物源性单胺水平的变化。所获得的结果以及本实验室其他研究的结果表明,所研究的吡咯烷衍生物可被视为新型阿尼西坦类似物,可改善记忆过程。这种作用根据所研究化合物的应用方式、实验动物的记忆能力以及所使用的实验方法而有很大差异。所研究物质引起的脑神经传递变化在其作用机制中起重要作用。