PHARMACOLOGICAL CHARACTERIZATION OF OPIATE PHYSICAL DEPENDENCE IN THE ISOLATED ILEUM OF THE GUINEA‐PIG

Abstract

1 Physical dependence was produced in ilea from naive guinea-pigs by exposure of the tissues to different opiates for logarithmically-spaced periods of time (20–320 min). The responsiveness of the tissue to naloxone, as indicated by a strong contracture of the ileum, was enhanced in contrast to that found in intestines not exposed to opiates. 2 The dose-response curves to naloxone obtained in tissues individually exposed to different opiates showed that their relative potency in increasing sensitivity to naloxone was as follows: levorphan > morphine > Met-enkephalin > nalorphine > pentazocine. 3 The naloxone-induced response was dose-dependent and was directly related to the opiate concentration and length of exposure. 4 Dextrorphan, the inactive isomer of levorphan, did not increase the responsiveness of the tissues to the narcotic antagonist, indicating that the phenomenon is stereospecific. 5 The naloxone-induced contraction in ilea exposed for 320 min to morphine (1 × 10⁻⁶ m) was not prevented or suppressed by the administration of a large dose of morphine (1 × 10 ⁻⁵ m) before or immediately after the naloxone challenge. 6 The evidence presented here shows that a phenomenon resembling in vivo opiate physical dependence can be acutely produced in vitro with pharmacological characteristics similar to other naloxone-induced abstinence effects.