Georgieva J, Danchev N
Department of Pharmacology and Toxicology, Medical Academy, Sofia, Bulgaria.
Methods Find Exp Clin Pharmacol. 1990 Dec;12(10):679-83.
Using pentylenetetrazol (PTZ) in subconvulsant doses, it was found that the semisynthetic diterpene sclareol glycol (SG) from the labdane family of diterpenes at a dose well below the lethal dose, although not being convulsant, had a proconvulsant action in mice. This action is indicated by the number of mice undergoing convulsions and the reduction of latency. Specific binding of [3H]-diazepam in vitro to whole homogenate fractions prepared from hippocampus of rats was not inhibited by SG. At the same time comparatively investigated Ro 15-1788 inhibited [3H]-diazepam binding. It is suggested that the proconvulsant effect of SG is realized not through interactions with central benzodiazepine receptors as Ro 15-1788 does, but perhaps through interactions with adenylate cyclase (stimulating its catalytic subunit and thus increasing brain 3',5'-AMP availability). Other brain neurotransmitter systems (e.g., GABA) should also participate in realization of the proconvulsant effect of SG.
使用亚惊厥剂量的戊四氮(PTZ)时发现,来自半日花烷型二萜类的半合成二萜香紫苏二醇(SG),在远低于致死剂量的情况下,虽然本身不会引发惊厥,但对小鼠有促惊厥作用。这种作用通过发生惊厥的小鼠数量以及潜伏期的缩短得以体现。体外实验中,SG并未抑制[3H] - 地西泮与大鼠海马制备的全匀浆组分的特异性结合。与此同时,对Ro 15 - 1788进行比较研究发现,它能抑制[3H] - 地西泮的结合。这表明,SG的促惊厥作用并非像Ro 15 - 1788那样通过与中枢苯二氮䓬受体相互作用来实现,而是可能通过与腺苷酸环化酶相互作用(刺激其催化亚基,从而增加脑内3',5'-AMP的可用性)来实现。其他脑内神经递质系统(如GABA)也应参与了SG促惊厥作用的实现过程。