Actions of prostanoids to induce emesis and defecation in the ferret.
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.
Kan
Kelvin K W
KK
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., SAR, Hong Kong, China.
Jones
Robert L
RL
Ngan
Man-Pui
MP
Rudd
John A
JA
D000818:Animals; D003672:Defecation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000009:adverse effects / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D013329:Structure-Activity Relationship; D014839:Vomiting / Q000139:chemically induced / Q000378:metabolism*
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011982:Receptors, Prostaglandin