Pharmacological characterization of opiate physical dependence in the isolated ileum of the guinea-pig.
1 Physical dependence was produced in ilea from naive guinea-pigs by exposure of the tissue 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 greater than morphine greater than Met-enkephalin greater than nalorphine greater than 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 x 10(-6)M) was not prevented or suppressed by the administration of a large dose of morphine (1 x 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.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D007981:Levorphanol / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009269:Nalorphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics; D010423:Pentazocine / Q000494:pharmacology; D019966:Substance-Related Disorders; D013997:Time Factors
D004745:Enkephalins; D009294:Narcotics; D007981:Levorphanol; D009270:Naloxone; D004744:Enkephalin, Methionine; D009020:Morphine; D010423:Pentazocine; D009269:Nalorphine