Present status and future perspectives of muscarinic receptor antagonists

Conventional anticholinergics (better called muscarinic antagonists) do not differentiate between subtypes of muscarinic receptors and cause unpleasant side-effects in peptic ulcer treatment. Pirenzepine, the first M1-receptor antagonist, has more selective inhibitory properties on oxyntic gastric glands and accelerates healing rates in peptic ulcer. Pirenzepine and H2-receptor antagonists interact synergistically on parietal cell function; their combination seems to be of therapeutic advantage in defined indications. Telenzepine, a pirenzepine analogue with a modified tricycle and M1-receptor selectivity, is about 10 to 25 times more potent than pirenzepine in reducing basal and stimulated gastric acid secretion in man. In patients with duodenal ulcer 3 mg telenzepine nocte seems to be as effective as 50 mg pirenzepine twice daily in regard to ulcer healing and pain relief. Another pirenzepine analogue with a modified side-chain (AF-DX 116) proved to be cardioselective in animal pharmacology, and was characterized as an M2-receptor antagonist. This might be an important step for a more profound understanding of structure-activity relationships of muscarinic receptor antagonists.