Anticonvulsant and neurotoxic effects of tetrahydrocannabinol stereoisomers.
Enantiomers of delta-6-tetrahydrocannabinol (THC), delta-6-THC-1'', 1''-dimethylheptyl (DMHP), and 7-OH-delta-6-THC-1'',1''-DMHP were assessed for their ability to block audiogenic seizures in genetically epilepsy-prone rats. The stereoisomers were evaluated also for their ability to produce differential neurotoxicity in the rat rotorod (ROT) paradigm. Potency comparisons among the compounds revealed modest to profound stereoselectivity for anticonvulsant and neurotoxic activities, a general increase in both activities with the DMHP and 7-OH modifications of delta-6-THC, and some favorable separation between anticonvulsant and neurotoxic activities with selected THC analogs.
Consroe
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Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721.
Mechoulam
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D000818:Animals; D000927:Anticonvulsants; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004827:Epilepsy / Q000188:drug therapy; D008297:Male; D009420:Nervous System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D013759:Dronabinol