Peripheral antagonistic action of trimebutine and kappa opioid substances on acoustic stress-induced gastric motor inhibition in dogs.
The effects of intracerebroventricular (i.c.v.), intravenous (i.v.) and oral (p.o.) administration of trimebutine on the gastric motor inhibition induced by acoustic stress were investigated in fasted dogs fitted with strain-gauge transducers on the antrum and proximal jejunum. Started 40-50 min after the last migrating motor complex, a 1 h acoustic stress delayed by 111% the occurrence of the next gastric migrating motor complex without affecting the jejunal motor pattern. This inhibition of gastric migrating motor complex induced by acoustic stress was abolished by previous p.o. administration of trimebutine (1 mg/kg) but not by its i.v. (0.1 mg/kg) or i.c.v. (0.01 mg/kg) injection. The trimebutine blockade of gastric motor alterations induced by acoustic stress was suppressed after previous i.v. treatment with MR 2266 (0.3 mg/kg) but was unaffected by naloxone (0.3 mg/kg). Furthermore oral administration of U-50488H (10 micrograms/kg) and ethylketocyclazocine (10 micrograms/kg) respectively abolished and reduced the acoustic stress-induced delay of the occurrence of the gastric migrating motor complex. We concluded that trimebutine is able to antagonize the gastric motor disturbances induced in dogs by acoustic stress, probably by acting selectively on peripheral kappa receptors located in the wall of the proximal gut and directly stimulated from a mucosal site.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000161:Acoustic Stimulation; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001575:Benzomorphans / Q000494:pharmacology; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D016314:Ethylketocyclazocine; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D013315:Stress, Psychological / Q000378:metabolism*; D014287:Trimebutine / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D000701:Analgesics, Opioid; D001565:Benzoates; D001575:Benzomorphans; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C027247:MR 2266; D016314:Ethylketocyclazocine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D003496:Cyclazocine; D014287:Trimebutine