Potential long acting opiate antagonists: preparation, pharmacological activity, and opiate-receptor binding of N-substituted 2'-hydroxy-5-methyl-9 alpha-propyl-6,7-benzomorphans.
A homologous series of N-substituted 2'-hydroxy-5-methyl-9 alpha-propyl-6,7-benzomorphans (hydrogen to octyl inclusive, allyl, and cyclopropylmethyl) was prepared. In contradistinction to the normetazocine, normorphine, and (-)-3-hydroxymorphinan series, the N-pentyl and N-hexyl derivatives do not have the analgesic potency of the parent N-methyl compound; instead, they are narcotic antagonists with a long duration of action. All of the N-substituted 9 alpha-propylbenzomorphans, except for methyl, heptyl, and octyl, have antagonist activity. The receptor binding constants of the N-alkyl compounds are uniformly two- to threefold lower than those of the N-substituted normetazocines.
D000700:Analgesics; D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D000882:Haplorhini; D006801:Humans; D066298:In Vitro Techniques; D009019:Morphinans / Q000138:chemical synthesis*; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced; D013997:Time Factors
D000700:Analgesics; D001575:Benzomorphans; D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009020:Morphine