Influence of the M1-receptor antagonists telenzepine and pirenzepine on pancreatic secretory response to intraduodenal tryptophan in dogs

Abstract

In conscious dogs with gastric and pancreatic fistulas, we compared the action of different doses of telenzepine (ranging from 9 to 243 nmol kg-1 h-1 i.v.) and pirenzepine (ranging from 43 to 1,170 nmol kg-1 h-1 i.v.) on the pancreatic secretory response to graded loads of intraduodenal infusions of tryptophan, given with a secretin background. Both, telenzepine and pirenzepine caused an overall significant inhibition of the cumulative incremental pancreatic protein output by 65.8 and 66.8%, respectively. The pancreatic bicarbonate output was also reduced by 38.3 and 40.5%, respectively, but the effect did not reach statistical significance. The inhibitory potency of the effective doses of telenzepine or pirenzepine did not differ significantly. Only the highest doses of telenzepine (243 nmol kg-1 h-1 i.v.) and of pirenzepine (1,170 nmol kg-1 h-1 i.v.) significantly increased heart rate from 59.9 +/- 3.4 to 63.1 +/- 4.5 bpm, respectively. These findings indicate that (1) in the intact animal, the M1-receptor antagonists telenzepine and pirenzepine are capable of inhibiting pancreatic bicarbonate and protein output in response to intraduodenal tryptophan with secretin background, and (2) telenzepine is 4.7 times more potent than pirenzepine.