Comparison of telenzepine, pirenzepine and atropine on gastric acid and pepsin secretion in response to histamine, pentagastrin, bethanechol, sham-feeding and feeding.
This study was designed to compare gastric antisecretory effects of telenzepine, a new antimuscarinic agent, with those of pirenzepine and atropine in dogs. None of these antimuscarinics affected gastric acid secretion induced by histamine but all of them caused a dose-dependent inhibition of acid secretion from the gastric fistula (GF) and Heidenhain pouches (HP) stimulated by pentagastrin and bethanechol, telenzepine being 5-9 times more potent than pirenzepine and equipotent with atropine. All antimuscarinics were also effective inhibitors of acid responses to sham feeding and ordinary feeding. The inhibitory effect of telenzepine and pirenzepine were not accompanied by any major alterations in plasma gastrin or somatostatin but those of atropine were related to significant increase in plasma gastrin and to significant decrease in plasma somatostatin levels, suggesting the involvement of M2 receptors in the cholinergic control of these hormones. All three antimuscarinics were effective inhibitors of pepsin secretion induced both from the GF and HP by all secretagogues used. Neither telenzepine nor pirenzepine administered in various doses affected the heart rate while atropine caused a significant increase in heart rate confirming that the former agents are selective M1 receptor antagonists. This study provides evidence that telenzepine is more potent than pirenzepine in the inhibition of gastric secretion induced by pentagastrin, bethanechol, sham-feeding and ordinary feeding and that, unlike atropine, it does not increase plasma gastrin responses to meat feeding. In fact, telenzepine and pirenzepine alike reduced plasma gastrin concentrations under these conditions. No influence of these antimuscarinics on plasma somatostatin levels was observed.
Konturek
S J
SJ
Institute of Physiology, Academy of Medicine, Krakow, Poland.
Tasler
J
J
Cieszkowski
M
M
Szewczyk
K
K
Kromer
W
W
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D004285:Dogs; D005502:Food; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula / Q000503:physiopathology; D006632:Histamine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology; D010434:Pepsin A / Q000378:metabolism*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013270:Stomach / Q000502:physiology
D001626:Bethanechol Compounds; D010276:Parasympatholytics; D018723:Bethanechol; C046338:telenzepine; D010890:Pirenzepine; D001285:Atropine; D006632:Histamine; D010434:Pepsin A; D010418:Pentagastrin