Pharmacodynamic evaluation of selective antimuscarinic properties of pirenzepine in the rat

Summary Central and peripheral antimuscarinic properties of pirenzepine following either oral or intravenous administration were evaluated in the rat, in comparison to atropine. Pirenzepine, unlike atropine, was shown to be devoid of central effects and to possess a marked selectivity toward the gastric muscarinic receptors. This selectivity is mainly directed toward the stomach: gastric ulcer and acid secretion inhibition can be achieved at lower doses than other secretions (salivation, lachrymation). Particularly, the oral ED 50 values of pirenzepine for inhibiting oxotremorine induced gastric ulcer and salivation were 0.4 mg/kg and 30 mg/kg, respectively orally, 13 and 620 μg/kg respectively by intravenous administration. On the other hand the ED 50 values of atropine for inhibiting the same parameters were 30 μg/kg and 550 μg/kg orally and 5.8 and 4.2 μg/kg intravenously. The ratios of the intravenous ED 50 values inhibiting the other measured symptoms to the therapeutic (anti-ulcer) effect were: o 1) pirenzepine — 11 for lachrymation, 48 for salivation, greater than 2308 for tremors, 2) atropine — 1.1 for lachrymation, 0.7 for salivation, 14 for tremors. These findings are discussed, in the attempt to correlate them with data of binding affinity studies.