Comparative effects of ketanserin, atropine and methysergide on the gastrointestinal effects of hyperserotoninemia in the awake dog.

Intestinal handling of water and electrolytes and motility were monitored in conscious dogs with chronic 25-cm Thiry-Vella loops of proximal jejunum. Absorption/secretion was quantitated using a neutral isosmotic perfusate containing [14C]polyethylene glycol as a recovery marker. Under basal conditions the animals absorbed water, Na+ and Cl-, while there was no net action on K+. Intravenous serotonin infusion (30 micrograms/kg/min) increased circulating levels of serotonin to a mean of 1556 +/- 191 ng/ml within 15 min of the commencement of the infusion. The infusion induced a significant secretion of water (mean -73 +/- 7 microliters/min) and electrolytes (sodium -10.4 +/- 0.7 muEq/min; potassium -0.8 +/- 0.05 muEq/min; chloride -12.4 +/- 1.0 muEq/min) in the dogs and all showed signs of hyperserotoninemia (salivation, loose bowel movements, tachypnea). After administration of ketanserin (33 micrograms/kg/min), a significant reduction in secretion was demonstrated (water +20.8 +/- 16.1 microliters/min; sodium 7.2 +/- 3.0 muEq/min; potassium -0.02 +/- 0.1 muEq/min; and chloride -1.9 +/- 2.8 muEq/min) as well as reduced motor activity. A similar antisecretory effect was demonstrated with atropine infusion (20 micrograms/kg/min), although this drug had a far more significant effect on the gastrointestinal motility recorded in the loop. Infusion of methysergide (33 micrograms/kg/min) did not significantly affect secretion (water -111.4 +/- 59.0 microliter/min; sodium -17.4 +/- 9 muEq/min; potassium -0.9 +/- 0.4 muEq/min; chloride -20.3 +/- 7.0 muEq/min). These results suggest possible actions which may make ketanserin useful in the treatment of symptoms of the carcinoid syndrome.