Possible involvement of peripheral serotonin 5-HT3 receptors in fluvoxamine-induced emesis in Suncus murinus.
Selective serotonin reuptake inhibitors fluvoxamine and fluoxetine, as well as serotonin (5-HT), induced vomiting in Suncus murinus (a house musk shrew). Fluvoxamine- and fluoxetine-induced vomiting gradually decreased with their repeated administration. Vomiting induced by serotonin also decreased with repeated treatment with serotonin. In these shrews, fluvoxamine-induced vomiting was partially inhibited. Fluvoxamine might induce vomiting, at least partially, by indirectly activating peripheral 5-HT(3) receptors, since serotonin has been reported to induce vomiting by activating peripheral 5-HT(3) receptors and granisetron, a 5-HT(3) antagonist, partially suppressed fluvoxamine-induced vomiting in our previous finding. In addition, fluvoxamine-induced vomiting was impaired more effectively using a step-wise dose-up schedule of fluvoxamine than a fixed high-dose schedule. Therefore, a careful dosing strategy starting with a low dose might be effective for avoiding emesis associated with the clinical use of fluvoxamine.
Fujiwara-Sawada
Mina
M
Pharmaceutical Research Center, Meiji Seika Kaisha Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan.
Imanishi
Taiichiro
T
Yoshida
Akiko
A
Baba
Jun
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects*; D016666:Fluvoxamine / Q000009:adverse effects*; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D012788:Shrews; D014839:Vomiting / Q000139:chemically induced*
D005473:Fluoxetine; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors