Pharmacological Actions of the Racemic and the Enantiomeric 1,4-Dimethyl-IO-Hydroxy-2,3,4,5,6,7-Hexahydro-1,6-Methano-IH-4-Benzazonines (C-Homobenzomorphans)

Abstract

Abstract-The racemate and optical isomers of the C-homobenzomorphans, 1,4 -dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine, were evaluated in a number of assays sensitive to narcotics of different types.All three C-homobenzomorphans were active in vitro in guinea pig ileum, mouse vas deferens, and rat brain membrane binding assays, but were of low potency. These C-homobenzomorphans showed different profiles of in vivo activity. The (+)-isomer and racemate were active as agonists in the tail-flick assay, whereas the (-)-isomer was inactive. At higher doses, the (-)-isomer and the racemate behaved as antagonists of morphine in the tail-flick assay. All three compounds were active in the phenylquinone test, but naloxone did not block this effect . In addition, all three were potent in the hot-plate test. Neither of the isomers sub stituted for morphine in dependent rats or monkeys. However, the (+)-isomer precipitated withdrawal in these monkeys.The (-)-isomer produced opioid-like physical dependence in both rats and monkeys.Some of the implications regarding the results with these remarkable homobenzomorphans are discussed.