对来自三白草的潜在抗精神病药物马兜铃亭A的初步评估。

Preliminary evaluation of manassantin A, a potential neuroleptic agent from Saururus cernuus.

作者信息

Rao K V, Puri V N, Diwan P K, Alvarez F M

机构信息

Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610.

出版信息

Pharmacol Res Commun. 1987 Sep;19(9):629-38. doi: 10.1016/0031-6989(87)90117-2.

DOI:10.1016/0031-6989(87)90117-2

PMID:2893391

Abstract

Manassantin A (MNS-A), a novel dineolignan isolated from Saururus cernuus was evaluated for its central depressant effects. Intraperitoneal (IP) administration of MNS-A to mice at nontoxic doses caused a decrease in spontaneous motor activity and inhibition of amphetamine-induced stereotypy, with an ED50 of 0.21 +/- 0.02 mg/kg for its antiamphetamine activity. Doses of MNS-A up to the LD50 did not produce catalepsy and ptosis as were observed with haloperidol used as a reference drug. The compound caused a dose-dependent hypothermia, while haloperidol was not very effective in this test. Potentiation of pentobarbital-sleeping time was observed to be of comparable degree with both drugs. In spite of the higher toxicity (acute LD50 5.4 +/- 0.2 mg/kg, IP) than that shown by haloperidol, the somewhat selective neuroleptic profile of MNS-A makes it an interesting candidate for more detailed studies.

摘要

从三白草中分离出的一种新型双新木脂素——马纳桑亭A（MNS - A），对其中枢抑制作用进行了评估。以无毒剂量腹腔注射（IP）给小鼠MNS - A后，可导致自发运动活动减少，并抑制苯丙胺引起的刻板行为，其抗苯丙胺活性的半数有效剂量（ED50）为0.21±0.02mg/kg。高达半数致死量（LD50）的MNS - A剂量并未产生如用作参考药物的氟哌啶醇所观察到的僵住症和眼睑下垂。该化合物可引起剂量依赖性体温过低，而氟哌啶醇在该试验中效果不佳。观察到两种药物对戊巴比妥睡眠时间的增强作用程度相当。尽管MNS - A的毒性（急性腹腔注射LD50为5.4±0.2mg/kg）高于氟哌啶醇，但其某种程度的选择性抗精神病特性使其成为更详细研究的一个有趣候选物。