Present status and future perspectives of muscarinic receptor antagonists.

Abstract

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.

• Authors: W Londong
• Journal: Scandinavian journal of gastroenterology. Supplement (Scand J Gastroenterol Suppl) Vol. 125 Pg. 55-60 ( 1986) ISSN: 0085-5928 [Print] England
• PMID: 2881347 (Publication Type: Journal Article)

Chemical References

• Histamine H2 Antagonists
• Parasympatholytics
• telenzepine
• Pirenzepine
• otenzepad

Topics

• Animals
• Drug Therapy, Combination
• Gastric Acid (metabolism)
• Histamine H2 Antagonists (therapeutic use)
• Humans
• Parasympatholytics (therapeutic use)
• Parietal Cells, Gastric (drug effects)
• Peptic Ulcer (drug therapy)
• Pirenzepine (analogs & derivatives, pharmacology, therapeutic use)