Potent analgetics derived from 9-nor-9 beta-hydroxyhexahydrocannabinol.
Based on the report of morphine-like analgetic activity of 9-nor-9 beta-hydroxyhexahydrocannabinol (HHC), we undertook a study of structural modifications of the C-3 side chain of HHC to optimize the analgetic activity. We ultimately examined four distinct classes of side chains: (1) alkyl (la-lc), (2) arylalkyl (ld-lh), (3) alkoxy (li-lj) and (4) arylalkyloxy (lk-lo). Three of these derivatives (lb, lf, ll) possessed analgetic activity 10X morphine. These studies demonstrate that the C-3 side chain of HHC can be modified in a structure-dependent fashion to yield potent, nonopioid analgetics. In addition, the effect of the 1 methyl-4-phenylbutyloxy side chain is unique among the side chains examined.
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D002187:Cannabinol / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology
D000701:Analgesics, Opioid; D002186:Cannabinoids; C014043:9-hydroxy-9-norhexahydrocannabinol; D009020:Morphine; D002187:Cannabinol; D001241:Aspirin; D010423:Pentazocine