Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 544, Issue 1-3, Pages 153-159Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2006.06.034
Keywords
prostanoid; emesis; defecation; ferret; NK1; 5-HT3
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In the present studies we investigated the mechanism of action of prostaglandin E-2 (1 mg/kg, i.p.) to induce emesis and defecation and/or tenesmus in the ferret. The emesis was antagonized significantly (P < 0.05) by ondansetron (0.3 and 1 mg/kg, i.p.) and (+)-(2S,3S)-3 -(2-methoxybenzylamino)2-phenlypiperidine hydrochloride (CP-99,994; 10 mg/kg, i.p.), but neither compound reduced defecations and/or tenesmus, with ondansetron (0.3 mg/kg) actually producing a slight increase (P < 0.05). Droperidol (1 and 3 mg/kg), metoclopramide (0.3 and 3 mg/kg), domperidone (0.3 and 3 mg/kg), promethazine (0.3 and 3 mg/kg) and scopolamine (0.3 and 3 mg/kg) failed to reduce prostaglandin E-2 induced emesis. However, droperidol (1 and 3 mg/kg) and scopolamine (0.3 and 3 mg/kg) reduced significantly the defecatory and/or tenesmus response (P < 0.05). Bilateral abdominal vagotomy was ineffective to reduce emesis and defecations and/or tenesmus. The data suggests that 5-HT3 receptor and NK1 tachykinin receptor antagonists could be useful in the clinic to prevent emesis but not defecations induced by prostaglandin E-2. (c) 2006 Elsevier B.V. All rights reserved.
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