Effects of nalbuphine, pentazocine and U50488H on gastric emptying and gastrointestinal transit in the rat.
We studied the effect of mixed agonist-antagonist opioids (nalbuphine and pentazocine) and a kappa opioid agonist (U50488H) on gastric emptying and gastrointestinal transit, and their interactions with morphine in rats. In each group, nalbuphine (0.01-30 mg kg-1), pentazocine (1-30 mg kg-1), U50488H (1-100 mg kg(-1)1) or saline was injected i.p. at 0 min. Another four groups of rats received morphine 13.4 mg kg-1 (ED75) and one of the following substances: saline, nalbuphine, pentazocine or U50488H. In both groups, at 30 min, radiolabelled saline 1 ml was infused into the stomach; at 1 h, gastric emptying and gastrointestinal transit were calculated by measuring the radioactivity in the gastrointestinal tract. Slopes for dose-response curves were determined. Nalbuphine significantly, but only weakly, delayed gastric emptying (P < 0.0005) and gastrointestinal transit (P < 0.01). Pentazocine markedly inhibited both, whereas U50488H did not significantly inhibit either. The slopes of the dose-response curves for nalbuphine, but not for pentazocine, on both gastric emptying and gastrointestinal transit were significantly less steep than those for morphine. Nalbuphine significantly antagonized the inhibitory effect of morphine on gastric emptying (P = 0.005) and gastrointestinal transit (P = 0.02), whereas pentazocine and U50488H did not. Nalbuphine and pentazocine delay gastric emptying and gastrointestinal transit, possibly by different mechanisms.
Department of Anaesthesiology, Kansai Medical University, Osaka, Japan.
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005746:Gastric Emptying / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D008297:Male; D009266:Nalbuphine / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009266:Nalbuphine; D010423:Pentazocine