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.
D000818:Animals; D004359:Drug Therapy, Combination; D005744:Gastric Acid / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D010276:Parasympatholytics / Q000627:therapeutic use*; D010295:Parietal Cells, Gastric / Q000187:drug effects; D010437:Peptic Ulcer / Q000188:drug therapy*; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*
D006635:Histamine H2 Antagonists; D010276:Parasympatholytics; C046338:telenzepine; D010890:Pirenzepine; C048593:otenzepad