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UM-1037 (3-allyl-1, 2, 3, 4, 5, 6-hexahydro-8-hydroxy-6-methyl-3-benzazocine), a benzazocine compound related structurally to the narcotic antagonists cyclazocine and the N-allyl analogue of cyclazocine, SKF-10,047, but lacking the 2,6-methano bridge, has been found to produce similar signs in normal rhesus monkeys to those characteristic of the narcotic abstinence syndrome1. Narcotic antagonists have been reported to produce contraction in the isolated guinea pig ileum2,3. However, only when the ileum has been continuously exposed to morphine or related drugs in vitro or has been isolated from animals made dependent on a narcotic, does it contract when an antagonist such as naloxone is added to the perfusion medium4. Thus, this preparation has been used as an in vitro model of the narcotic abstinence syndrome, and the contraction might be considered an ‘abstinence sign’. In the present study, UM-1037 was found to produce a contraction of the guinea pig ileum isolated from normal animals similar to the contraction produced by naloxone in preparations exposed to morphine or related drugs. UM-1037, like naloxone, seems to act by releasing acetylcholine (ACh), because its actions were antagonised by atropine and tetrodotoxin. However, morphine, which is necessary for the naloxone-induced contraction, reversed the effect of UM-1037 on the ileum. Responses to UM-1037 were not altered in the presence of naloxone. Thus, the release of ACh which is produced by this unusual benzazocine in the ileum does not seem to be mediated by the opiate receptor.

An unusual benzazocine elicits acetylcholine release in the isolated guinea pig ileum