Pharmacological evaluation of agonistic and antagonistic activity of cannabinoids.
The behavioral effects of cannabinoids are dependent upon numerous variables which include species differences, dose, experimental conditions, etc. The complexity of the cannabinoid behavioral syndrome certainly complicates attempts to establish biochemical correlates. It is for this reason that attempts are being made to develop analogs that exhibit selective behavioral effects. The pharmacological profile of the analogs that exhibit selective behavioral effects. The pharmacological profile of the analogs summarized in table 6 suggests a tentative classification for the cannabinoids. While there are numerous analogs which produce the entire spectrum of cannabinoid effects, only those discussed within this article are grouped in class 1. CBD and many of its analogs appear to be devoid of cannabinoid effects, but they are capable of producing CNS depression at large doses (class 2). It is our working hypothesis that the compounds in class 2 may be altering membrane peturbation in a nonspecific fashion. This latter effect may or may not be related to the psychoactive cannabinoids. Class 3 compounds are potent CNS depressants that appear to lack other effects that are unique to cannabinoids. These analogs are particularly interesting in that they may be altering membrane function i a specific fashion in contrast to nonspecific effects exerted by analogs in class 2. Analogs in class 4 appear to exert selective CNS depression. While the mechanism by which these analogs are producing their effects may be proven to be different from those postulated, it does appear that a classification of cannabinoid effects is possible through structural alterations in the cannabinoid molecule.
Martin
B R
BR
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0001.
Compton
D R
DR
Little
P J
PJ
Martin
T J
TJ
Beardsley
P M
PM
D000700:Analgesics; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002186:Cannabinoids / Q000494:pharmacology*; D002492:Central Nervous System Depressants; D003216:Conditioning, Operant / Q000187:drug effects; D004285:Dogs; D013759:Dronabinol / Q000037:antagonists & inhibitors*; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008566:Membranes / Q000187:drug effects*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000700:Analgesics; D002186:Cannabinoids; D002492:Central Nervous System Depressants; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol