Neuronally mediated contraction responses of guinea-pig stomach smooth muscle preparations: modification by benzamide derivatives does not reflect a dopamine antagonist action.
The actions of the substituted benzamide derivatives metoclopramide, clebopride, YM-09151-2, tiapride, (+)- and (-)-sulpiride and (+)- and (-)-sultopride, and the dopamine antagonists haloperidol and domperidone, were studied on the responses to field stimulation (0.125-10 Hz) of smooth muscle strips taken from cardia, fundus, body and antral regions of the longitudinal and circular muscle of guinea-pig stomach. Field stimulation of the longitudinal strips caused contraction responses which were antagonised by atropine (but not by prazosin, yohimbine, propranolol or methysergide) to indicate a muscarinic cholinergic involvement. Antagonism of the contractions revealed or enhanced relaxation responses mediated via unidentified mechanisms (resistant to cholinergic and adrenergic antagonists). Metoclopramide enhanced the field stimulation-induced contractions of the stomach smooth muscle preparations via atropine sensitive mechanisms but failed to attenuate the field stimulation-induced relaxation responses. Clebopride's action closely followed that of metoclopramide but YM-09151-2 only enhanced the contraction responses of the longitudinal muscle preparations. Other dopamine antagonists, (+)- and (-)-sulpiride, (+)- and (-)-sultopride, tiapride, haloperidol and domperidone failed to facilitate contraction to field stimulation of any stomach tissue. Thus, the actions of metoclopramide, clebopride and YM-09151-2 to facilitate contraction to field stimulation of stomach smooth muscle are mediated via a muscarinic cholinergic mechanism and are not the consequence of an antagonism at any recognisable dopamine receptor.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D004294:Domperidone / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects / Q000294:innervation
D001549:Benzamides; D011954:Receptors, Dopamine; D004294:Domperidone; C014417:clebopride; D006220:Haloperidol; D008787:Metoclopramide; C030265:nemonapride