The new antisecretory
drug,
telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H-thieno-[3,4 - b][1,5]benzodiazepin-10-one), was investigated for its inhibition of functionally intact
muscarinic receptors involved in gastric acid secretion in rabbit fundic glands, perfused mouse stomach in vitro, perfused rat stomach in situ,
gastric fistula in rats and dogs with a Heidenhain pouch. The effects on these receptors were contrasted with effects on receptors located on smooth muscle and heart, i.e. isolated rat urinary bladder, stomach and atrium. The results were compared to those values obtained with nonselective
antimuscarinic drugs (
N-methylscopolamine,
atropine) and the selective M-1 antagonist
pirenzepine.
Telenzepine was found to be 4-10 times more potent than
pirenzepine with respect to depressing both gastric acid secretion and smooth muscle or myocardial responses. Based on -log EC50 and pA2 values, both drugs exhibited a similar selectivity profile differing from the pattern of effects observed with
atropine or a second reference compound, zolenzepine. As compared with
atropine,
telenzepine exhibited a 5 fold higher relative affinity to
muscarinic receptors involved in gastric acid secretion. It was concluded that
telenzepine is selective to discriminate between
muscarinic receptors mediating gastric acid secretion and affecting muscle contractility and that this finding supports the concept of
muscarinic receptor heterogeneity.