The effects of the diterpene sclareol glycol on seizures do not depend on central benzodiazepine receptors.
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.
Georgieva
J
J
Department of Pharmacology and Toxicology, Medical Academy, Sofia, Bulgaria.
Danchev
N
N
D000818:Animals; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology*; D005442:Flumazenil / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
D004224:Diterpenes; D011963:Receptors, GABA-A; D005442:Flumazenil; D010433:Pentylenetetrazole; C060464:sclareol glycol