title: Pharmacological actions of the racemic and the enantiomeric 1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benz azo nines (C-homobenzomorphans).
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-benzaz onine, 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 substituted 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.
mesh_terms: D000700:Analgesics; D000818:Animals; D001575:Benzomorphans / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D016227:Benzoquinones; D001667:Binding, Competitive / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005048:Etorphine / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism; D011809:Quinones; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism; D019966:Substance-Related Disorders
chemical_list: D000700:Analgesics; D001575:Benzomorphans; D016227:Benzoquinones; D009019:Morphinans; D011809:Quinones; C029322:phenylbenzoquinone; D005048:Etorphine