morphine-chloride and Substance-Related-Disorders

A series of 53 1-phenyl-6-azabicyclo[3.2.1]octanes (1) has been tested for their analgetic and narcotic antagonist activities. Structure-activity relationships were investigated by varying the structural parameters. The most interesting compound in this series, the 1-(3-hydroxphenyl)-6,7-dimethyl derivative 8, shows the profile of a well-balanced antagonist-analgesic agent with a very mild physical dependence capacity. The absolute stereochemistry of its active enantiomer [(+)8] was established by the x-ray study and the chemical transformation to the phenylmorphan [(+)-II]. (+)-8 was stereochemically correlated also with the active enantiomer of the 7-demethyl derivatives [(+)-7] by chemical transformation and CD measurement. Certain structural and stereochemical correlations between these compounds (7 and 8) and other known antagonist-analgetics are discussed.

Topics: Analgesics; Animals; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Haplorhini; Humans; Lethal Dose 50; Macaca mulatta; Molecular Conformation; Nalorphine; Narcotic Antagonists; Rabbits; Stereoisomerism; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders; X-Ray Diffraction

The levo and dextro isomers of 2,5-dimethyl-2'-hydroxy-9alpha- and -9beta-propyl-6,7-benzomorphans have been prepared. The analgesic potency and physical dependence capacity of the optical isomers and their racemic parents were determined. The 9alpha-propyl levo isomer was analgesically equipotent with morphine; the 9beta-propyl levo isomer was considerably more potent subcutaneously and equipotent orally. None of the optical isomers suppressed the withdrawal syndrome; the 9beta-propyl levo isomer exacerbated the withdrawal syndrome.

Topics: Analgesics; Animals; Benzomorphans; Haplorhini; Humans; Mice; Morphinans; Morphine Dependence; Optical Rotation; Stereoisomerism; Substance-Related Disorders