CANNABIMIMETIC ACTIVITY FROM CP-47,497, A DERIVATIVE OF 3-PHENYLCYCLOHEXANOL

Abstract

CP-47,497 (cis-3-[2-hydroxy-4(1,1-dimethylheptyl)phenyl]-cyclohexan-1-ol) is characterized as a cannabimimetic agent, with 3-28 times greater potency than .DELTA.9-tetrahydrocannabinol (.DELTA.9-THC). In common with .DELTA.9-THC and other active structures closely related chemically to .DELTA.9-THC, CP-47,497 exerts analgesic, motor-depressant, anticonvulsant and hypothermic effects. It elicits vocalization in palpated rats and ataxia in dogs. In drug discrimination studies in rats, the stimulus properties of .DELTA.9-THC (3.2 mg/kg i.p.) are generalized to CP-47,497 with an absolute threshold dose 3-14 times lower than the threshold dose of .DELTA.9-THC itself, depending on route. Rats are unable to discriminate between the stimulus properties of equated i.p. doses of .DELTA.9-THC and CP-47,497 after prolonged training. Despite its potent behavioral effects. CP-47,497, like .DELTA.9-THC, does not resemble standard antipsychotic, antidepressant, antianxiety or hypnotic drugs in simple drug interaction tests. CP-47,497 exemplifies a simplified structure capable of producing many effects in common with those of .DELTA.9-THC and 9-normethyl-9.beta.-hydroxy-hexahydrocannabinol.