Actions of prostanoids to induce emesis and defecation in the ferret.

Abstract

Several prostanoids were investigated for their ability to induce emesis and/or defecation and tenesmus in the ferret. The rank order of emetic potency (dose producing four episodes, D4) was: sulprostone (5 microg/kg)>11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619; 8 microg/kg)>misoprostol (27 microg/kg)>17-phenyl-omega-trinor prostaglandin E2 (53 microg/kg)>prostaglandin E2 (94 microg/kg)>5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C; 148 microg/kg)>>prostaglandin F(2alpha) (13,500 microg/kg). Emesis was also induced by iloprost (D4 not determined) and prostaglandin E2 methyl ester (D4=350 microg/kg). Cicaprost and fluprostenol were virtually inactive; they also failed to modify copper sulphate (100 mg/kg, intragastric)-induced emesis (P>0.05), although cicaprost potentiated apomorphine (0.25 mg/kg, s.c.)-induced emesis (P<0.05). U46619-induced emesis was antagonised by vapiprost (P<0.05). The rank order of potency to produce defecation and tenesmus (dose producing three episodes) was: sulprostone (12 microg/kg)>misoprostol (15 microg/kg)>17-phenyl-omega-trinor prostaglandin E2 (94 microg/kg)>prostaglandin E2 (113 microg/kg)>fluprostenol (158 microg/kg)z.Gt;prostaglandin F(2alpha) (1759 microg/kg); prostaglandin E2 methyl ester also induced defecation (196 microg/kg). Data are discussed in relation to mechanisms involved in emesis and defecation.

• Authors: Kelvin K W Kan, Robert L Jones, Man-Pui Ngan, John A Rudd
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 453 Issue 2-3 Pg. 299-308 (Oct 25 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12398918 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Prostaglandin Antagonists
• Prostaglandins
• Receptors, Prostaglandin

Topics

• Animals
• Defecation (drug effects)
• Dose-Response Relationship, Drug
• Ferrets
• Male
• Prostaglandin Antagonists (pharmacology)
• Prostaglandins (adverse effects, pharmacology)
• Receptors, Prostaglandin (agonists, antagonists & inhibitors, physiology)
• Structure-Activity Relationship
• Vomiting (chemically induced, metabolism)