Drugs derived from cannabinoids. 1. Nitrogen analogs, benzopyranopyridines and benzopyranopyrroles.
Various nitrogen analogs of delta6a,10a-tetrahydrocannabinol were synthesized by a general procedure described in an earlier communication. Minimum effective doses (MED50's) and lethal doses (LD50's) were determined by a modified Irwin mouse screen after iv administration of compounds in PEG 200. The most potent compounds were the propargyl (5t), allyl (5m), and chloroallyl (5o-q) derivatives. Overt behavioral effects (CNS depression, static ataxia, and hypersensitivity) of 5t and Roger Adams' carbocyclic analog (III) were found to be similar in the mouse, cat, dog, and monkey. Dichloroisoproterenol prevented and reversed many of the depressant effects of both III and 5t but had no effect on the ataxia produced by these compounds. In antinociceptive tests, 5t was active in the phenylquinone and Eddy hot-plate tests but was inactive in the tail-flick test.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002188:Cannabis / Q000138:chemical synthesis*; D002415:Cats; D004285:Dogs; D013759:Dronabinol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D009021:Morphine Dependence / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects; D009541:Nictitating Membrane / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D012018:Reflex / Q000187:drug effects; D013329:Structure-Activity Relationship
D001578:Benzopyrans; D011725:Pyridines; D011758:Pyrroles; D013759:Dronabinol