Comparison of the gastric antisecretory and antiulcer potencies of telenzepine, pirenzepine, ranitidine and cimetidine in the rat.
In different rat models, the antisecretory and antiulcer effects of the M1-antimuscarinics telenzepine and pirenzepine, the nonselective antimuscarinic atropine, and the H2-blockers ranitidine and cimetidine were compared to each other. Intravenous telenzepine proved to be more potent in inhibiting gastric acid secretion in the Ghosh-Schild rat (carbachol-stimulated), the chronic fistula rat (basal secretion), or, both intravenously and orally, in the modified Shay rat, as compared to pirenzepine, cimetidine or ranitidine. After intravenous administration, only atropine was equally potent to telenzepine in all three models, but it was less potent than telenzepine after oral administration in the modified Shay rat. Gastric mucosal lesions induced by pylorus ligation plus acetylsalicyclic acid or acetylsalicyclic acid plus HCl were best inhibited by telenzepine and atropine, with pirenzepine, ranitidine and cimetidine being less potent, their relative potencies depending on the particular experimental model used. Thus, among the antiulcer drugs tested, telenzepine was the most potent one with respect to both antisecretory and antiulcer activity. Moreover, the duration of the antiulcer effect of telenzepine proved to be significantly longer than that of pirenzepine in the modified Shay rat.
Riedel
R
R
Department of Pharmacology, Byk Gulden Research Laboratories, Konstanz, FRG.
Bohnenkamp
W
W
Eltze
M
M
Heintze
K
K
Prinz
W
W
Kromer
W
W
D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002927:Cimetidine / Q000627:therapeutic use; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D010276:Parasympatholytics / Q000627:therapeutic use*; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000627:therapeutic use; D011899:Ranitidine / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000188:drug therapy*
D000897:Anti-Ulcer Agents; D010276:Parasympatholytics; C046338:telenzepine; D010890:Pirenzepine; D002927:Cimetidine; D011899:Ranitidine