Abstract

Effects of the nonbenzamide 5-hydroxytryptamine₄ agonist SDZ HTF 919 on gastrointestinal motility are unclear. Our aim was to assess the in vivo effects on gastrointestinal and colonic transit of radiolabeled residue and on colonic phasic contractility. In six female dogs, transit was measured over a period of 2 days by radioscintigraphy and colonic motility was measured by pneumohydraulic perfusion manometry of the proximal and distal colon. SDZ HTF 919 was administered initially by bolus i.v. infusion, followed by s.c. injection 8 and 16 hr later. Doses tested were 0.03, 0.1 and 0.3 mg/kg, and isotonic saline and vehicle served as controls in each dog. Stomach and small bowel transit was not significantly altered by SDZ HTF 919. Overall, i.v. SDZ HTF 919 accelerated colonic transit during the first 1 hr, compared with controls. These effects were significant even with the lowest dose of SDZ HTF 919. Responses to higher infusion doses were more variable. SDZ HTF 919 did not cause significant changes in quantitative pressure indices, such as amplitude or motor index, in the small bowel or colon. Prolonged postprandial colonic contractions, each lasting >30 sec, were noted after each i.v. agent and were significantly more frequent with the 0.03 mg/kg dose than with control (vehicle) treatment. Thus, SDZ HTF 919 accelerates canine colonic transit in vivo during the first 1 hr after i.v. administration. SDZ HTF 919 appears to be a promising agent for stimulation of mammalian colonic transit.