EXOCRINE PANCREATIC-SECRETION IN MAN FOLLOWING ONE WEEK OF M(1)-MUSCARINIC RECEPTOR BLOCKADE

A double-blind, randomized, placebo-controlled crossover study was per formed to assess the influence of one week of selective M1-muscarinic receptor blockade on pancreatic exocrine secretion in man. Ten healthy subjects received telenzepine (3 mg p.o.) and placebo each for 8 days , with a 6-day drug-free washout interval between treatment sequences. On Day 8 of each sequence, pancreatic secretion was stimulated for 2 h by infusion of submaximal secretin (0.2 U.kg/h) followed by maximal stimulation with secretin (1.0 U.kg/h) and ceruletide (120 ng.kg/h). T elenzepine had no significant effect on secretory parameters during su bmaximal stimulation with secretin. During maximal stimulation, total protein, secretory volume, and output of amylase, trypsin and bicarbon ate were unexpectedly increased by telenzepine. These findings might b e partially explained by removal of the inhibitory influence of pancre atic polypeptide, which was depressed by telenzepine. Acute studies ha ve shown that M1-receptor antagonists inhibit exocrine secretion. Our results suggest that adaptation of physiological mechanisms governing the exocrine pancreas may occur after one week of receptor blockade by a therapeutic dosage of telenzepine, to the extent that M1-blockade n o longer inhibits secretion.