Effects of efonidipine hydrochloride (NZ-105) on gastrointestinal functions and experimental gastric ulcers in rats and dogs

The effects of efonidipine hydrochloride, a newly synthesized dihydropyridine derivative, on gastrointestinal functions and experimental ulcers were investigated in comparison with nicardipine hydrochloride. Efonidipine and nicardipine (3, 10, 30 mg/kg, p.o.) dose-dependently suppressed gastric acid output in pylorus-ligated rats. However, nicardipine (10 mg/kg, p.o.) significantly delayed rat gastric emptying, efonidipine at the same dose showed normal emptying. Gastrointestinal contractile activities were not apparently changed in response to efonidipine and nicardipine (2, 5, 10 mg/kg, i.g.) in force transducer implanted conscious dogs. Efonidipine (3, 10, 30 mg/kg, p.o.) had little influence on the development of several mucosal lesions in the stomach including stress-induced lesions. However, nicardipine, at doses above 3 mg/kg, obviously aggravated the development of HCl + ethanol and ammonia-induced gastric lesions. Cimetidine (30 mg/kg, p.o.), an H₂ antagonist, significantly inhibited the formation of stress-induced gastric lesions through its anti-secretory property. Efonidipine and nicardipine (3, 10, 30 mg/kg, p.o.) in combination treatment with cimetidine showed no influence on the action of cimetidine in stress-induced gastric lesions. These results suggest that efonidipine at doses which reduce hypertension has little influence on gastrointestinal motor functions and gastric mucosal defensive systems in contrast to nicardipine. The inhibition of gastric acid secretion by efonidipine seems to not show anti-ulcer effect. It may be said that efonidipine might be a useful and safe dihydropyridine derivative in treatment with hypertension.