Effects of a 5-hydroxytryptamine3 receptor antagonist (ICS 205-930) on colonic motor activity in healthy men.

1. ICS 205-930 (Sandoz) is a selective antagonist at 5-hydroxytryptamine3 receptors and exerts marked effects on gastrointestinal motility in animals. 2. This study investigated, under random double-blind conditions, the effects of 10 and 20 mg ICS 205-930 infused intravenously in comparison with placebo on colonic motor activity. 3. Twelve healthy men participated each in three studies in which they received, in random double-blind fashion, each of the treatments. Colonic pressures were recorded pneumohydraulically with four catheter orifices 20-40 cm from the anal verge. Treatments were administered after a basal 30 min. One hour later, subjects ingested a 4200 kJ meal and 90 min thereafter, 1 mg neostigmine was administered intramuscularly and recording continued for another 90 min. 4. After both doses of ICS 205-930, the number of contractions as averaged over the entire recording time was slightly but significantly higher than after placebo. 5. After 10 mg but not after 20 mg ICS 205-930, amplitude of contractions and area under the curve as averaged over the entire recording time were significantly higher than after placebo. 6. ICS 205-930 induced few and mild side effects, but significantly more self-rated drowsiness and tiredness than placebo.