Differential action of anti-emetic drugs on defecation and emesis induced by prostaglandin E2 in the ferret.
In the present studies we investigated the mechanism of action of prostaglandin E2 (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 E2 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 E2.
Kan
Kelvin K W
KK
Emesis Research Group, Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Rudd
John A
JA
Wai
Man K
MK
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D005289:Ferrets; D006632:Histamine / Q000378:metabolism; D008297:Male; D011954:Receptors, Dopamine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D014839:Vomiting
D000932:Antiemetics; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D044406:Receptors, Serotonin, 5-HT3; D018039:Receptors, Tachykinin; D006632:Histamine; D015232:Dinoprostone