Oxilorphan (l-N-cyclopropylmethyl-3,14-dihydroxymorphinan): a new synthetic narcotic antagonist.

Oxilorphan is a fully synthetic morphinan derivative containing the 14-hydroxy group characteristics of naloxone and naltrexone. As a narcotic antagonist, oxilorphan was 4 times more potent than dl-cyclazocine, equipotent to naloxone and about one-fourth as potent as naltrexone parenterally. Duration studies in rodents were inconclusive, but in antagonism of morphine analgesia and miosis in the dog, oxilorphan was longer acting than naloxone and equivalent to dl-cyclazocine. Oxilorphan was inactive in the conventional animal thermal analgesic tests. However, oxilone did exhibit relatively weak analgesic activity in preventing phenylquinone-induced abdominal contraction at doses about 700 times higher than those required for antagonist activity. The analgesic potency of oxilorphan was only 120 and 1/300 the potency of morphine and dl-cyclazocine, respectively, but was significantly greater than naltrexone and naloxone. Mice chronically treated with increasing doses of oxilorphan failed to exhibit withdrawal jumping after naloxone challenge. General central nervous system activity studies showed oxilorphan to be relatively free from central side effects at doses at which dl-cyclazocine produced pronounced effects.