Telenzepine, a new M1-receptor antagonist, is a more potent inhibitor of pentagastrin-stimulated gastric acid output than pirenzepine in dogs.
In conscious dogs with a gastric fistula we compared the action of different doses of telenzepine (ranging from 1 to 243 nmol/kg/h) and pirenzepine (ranging from 4.7 to 1170 nmol/kg/h) on gastric acid output in response to pentagastrin (1 to 8 micrograms/kg/h). Pentagastrin caused a dose-dependent increase in gastric acid output. A dose of 27 nmol/kg/h and all subsequent doses of telenzepine and a dose of 130 nmol/kg/h and all higher doses of pirenzepine significantly inhibited (up to 74% of control values) the gastric acid response to pentagastrin. Doses above 27 nmol/kg/h of telenzepine and doses above 130 nmol/kg/h of pirenzepine did not further inhibit the gastric acid output. Only the highest doses of telenzepine (243 nmol/kg/h) and pirenzepine (1170 nmol/kg/h) significantly increased heart rate from 66 +/- 3.1 to 77.1 +/- 3.9 and 72.5 +/- 3.2, respectively (beats/min, chi +/- SEM, n = 6). Differences between both drugs were not found with regard to cardiovascular responses of equipotent doses. We conclude that in conscious dogs with an intact stomach, the new M1-receptor antagonist telenzepine is, on a molar basis, more than 4.7 times more potent than pirenzepine in inhibiting pentagastrin-stimulated gastric acid output. This inhibition occurs at doses that do not increase heart rate, and, therefore, probably cause few systemic effects.
Holtmann
G
G
Dept. of Medicine, University of Essen, FRG.
Küppers
U
U
Singer
M V
MV
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology; D010890:Pirenzepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; C046338:telenzepine; D010890:Pirenzepine; D010418:Pentagastrin