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Comparison of the effects of metoclopramide on sympathetic and muscarinic responses after pretreatment with atropine and pirenzepine.

Metoclopramide (0.15 mg/kg i.v.) was administered to seven healthy volunteers after pretreatment with either atropine, pirenzepine or saline. With the i.v. doses of atropine (0.020 mg/kg) and pirenzepine (0.20 mg/kg) used in the study, antimuscarinic activities in serum were comparable for the most part of the study. Atropine induced a pronounced rise in heart rate and a hypotensive blood pressure response in the orthostatic test, whereas heart rate was significantly lower after pretreatment with pirenzepine than after saline, without any significant effects on systolic blood pressure. Plasma noradrenaline but not plasma adrenaline response to upright posture was increased after metoclopramide following saline but it was reduced following pirenzepine pretreatment, atropine having no significant effect on plasma noradrenaline response in the orthostatic test. Saliva secretion was lower after atropine than after pirenzepine or saline. Pirenzepine seems to diverge from classical anticholinergic drugs, and it reduces the metoclopramide-induced increase in sympathetic responsivity under conditions where cardiac function is not appreciably affected.