Rao K V, Puri V N, el-Sawaf H A
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610.
Eur J Pharmacol. 1990 Apr 25;179(3):367-76. doi: 10.1016/0014-2999(90)90177-8.
In an earlier preliminary study, manassantin A, a neolignoid from Saururus cernuus was found to show neuroleptic type activity in mice when given by the i.p. route. It blocked the stereotypy and hyperactivity caused by amphetamine at doses comparable to those of haloperidol, but unlike the latter, did not show catalepsy or ptosis at atoxic doses. In the present study, a more detailed comparison of manassantin A with haloperidol and in some cases with chlorpromazine and reserpine using a variety of neuroleptic parameters and by various routes of administration is described. Results of the present study clearly show that the drug is readily absorbed from various routes of administration and shows many of the patterns of neuroleptic activity. Manassantin A was comparable to haloperidol in many of the tests but unlike the latter, did not produce antiadrenergic or anticholinergic effects. Manassantin A was found to bind weakly to calf caudate membranes (IC50 3500 nM) while haloperidol (IC50 5 nM) and chlorpromazine (IC50 50 nM) inhibited [3H]haloperidol binding. Manassantin A also did not affect the dopamine-induced adenylate cyclase activity in rat caudate nuclei (IC50 greater than 10,000 nM) while haloperidol (IC50 700 nM) and chlorpromazine (IC50 350 nM) inhibited the enzyme synthesis. These biochemical and behavioral tests suggest that manassantin A exhibits a selective neuroleptic profile and may be considered to behave as an atypical agent.
在一项早期的初步研究中，发现来自三白草的新木脂素马纳桑亭A经腹腔注射给药时，在小鼠中表现出抗精神病样活性。它在与氟哌啶醇相当的剂量下阻断了苯丙胺引起的刻板行为和多动，但与后者不同的是，在无毒剂量下不表现出僵住症或眼睑下垂。在本研究中，描述了使用各种抗精神病参数并通过各种给药途径，将马纳桑亭A与氟哌啶醇以及在某些情况下与氯丙嗪和利血平进行更详细的比较。本研究结果清楚地表明，该药物可从各种给药途径快速吸收，并表现出许多抗精神病活性模式。马纳桑亭A在许多测试中与氟哌啶醇相当，但与后者不同的是，它不产生抗肾上腺素能或抗胆碱能作用。发现马纳桑亭A与小牛尾状核膜的结合较弱（IC50为3500 nM），而氟哌啶醇（IC50为5 nM）和氯丙嗪（IC50为50 nM）可抑制[3H]氟哌啶醇的结合。马纳桑亭A也不影响大鼠尾状核中多巴胺诱导的腺苷酸环化酶活性（IC50大于10000 nM），而氟哌啶醇（IC50为700 nM）和氯丙嗪（IC50为350 nM）可抑制该酶的合成。这些生化和行为测试表明，马纳桑亭A表现出选择性抗精神病特征，可被认为是一种非典型药物。
