Emesis and Defecations Induced by the 5-Hydroxytryptamine (5-HT3) Receptor Anatagonist Zacopride in the Ferret
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
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Three antiemetic compounds zacopride, batanopride, granisetron were evaluated for the production of gastrointestinal side effects in the conscious ferret after i.v. or p.o. administration. Zacopride evoked multiple emetic and defecatory responses at clinically relevant doses 0.003-0.3 mgkg and in a dose-dependent manner. The oral route was the more potent one for eliciting emesis ED50 0,033 mgkg. At 0.3 mgkg p.o., zacopride reliably evoked an 80 to 100 incidence of emesis and a 40 to 80 incidence of defecation. In contrast, batanopride and BRL43694 i.v. evoked a small 10 incidence of these side effects, but only at 0.1 to 10 mgkg doses. When give p.o. 0.00003-10mgkg, these latter compounds never evoked emesis and significantly reduced the incidence of defecation below that of vehicle. Responses to zacopride 0.3 mgkg p.o. were challenged by i.p. pretreatment with the 5-hydroxytryptamine receptor agonist 2-methyl serotonin, the 5-hydroxytryptamine receptor antagonist BRL43694, the quaternary atropine derivative glycopyrrolate, the dopamine receptor antagonist domperidone or selective abdominal vagotomies.
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