Abstract
In conscious dogs with a gastric fistula we compared the action of different doses of telenzepine (ranging from 1 to 243 nmol/kg/h) and pirenzepine (ranging from 4.7 to 1170 nmol/kg/h) on gastric acid output in response to pentagastrin (1 to 8 μg/kg/h). Pentagastrin caused a dose-dependent increase in gastric acid output. A dose of 27 nmol/kg/h and all subsequent doses of telenzepine and a dose of 130 nmol/kg/h and all higher doses of pirenzepine significantly inhibited (up to 74% of control values) the gastric acid response to pentagastrin. Doses above 27 nmol/kg/h of telenzepine and doses above 130 nmol/kg/h of pirenzepine did not further inhibit the gastric acid output. Only the highest doses of telenzepine (243 nmol/kg/h) and pirenzepine (1170 nmol/kg/h) significantly increased heart rate from 66 ± 3.1 to 77.1 ± 3.9 and 72.5 ± 3.2, respectively (beats/min, x ± SEM, n = 6). Differences between both drugs were not found with regard to cardiovascular responses of equipotent doses. We conclude that in conscious dogs with an intact stomach, the new M1-receptor antagonist telenzepine is, on a molar basis, more than 4.7 times more potent than pirenzepine in inhibiting pentagastrin-stimulated gastric acid output. This inhibition occurs at doses that do not increase heart rate, and, therefore, probably cause few systemic effects.