Effects of a new 1,4-dihydropyridine, lacidipine, on gastrointestinal motility and other gastrointestinal functions.

ABSTRACT

Lacidipine is a new 1,4-dihydropyridine calcium entry blocker endowed with slow onset of action and potent and long-lasting antihypertensive activity. This study investigated the effect of lacidipine on some gastrointestinal functions, mainly gastrointestinal motility, in rats and dogs. In fasting conscious dogs chronically fitted with electrodes and strain gauges along the small bowel, lacidipine (12 micrograms/kg i.v. bolus or 10 micrograms/kg/h for 3 h) did not modify the migrating motor complex pattern or intestinal spike activity. In the rat, lacidipine proved less active (ED 50 greater than 100 mg/kg p.o.) than nitrendipine (ED 50 = 31 mg/kg p.o.) in inhibiting gastric emptying of a liquid meal, whereas the opposite was true after a solid meal (ED 50 = 10.9 and 35.0 mg/kg p.o., respectively). Lacidipine inhibited fecal pellet output at lower doses (ED 50 = 14.8 mg/kg p.o.) than nitrendipine (ED 50 = 40.1 mg/kg p.o.). On histamine-induced gastric acid secretion, the effect of 100 micrograms/kg i.v. lacidipine was moderate (maximum inhibition 45%). The gastrointestinal effects displayed by lacidipine appear at doses at least 5 and 50 times as high as those affecting blood pressure after intravenous and oral administration, respectively. Thus, lacidipine is unlikely to cause noteworthy unwanted effects on the gastrointestinal tract.