Effects on nociception of the Ca2+ and 5-HT antagonist dotarizine and other 5-HT receptor agonists and antagonists.
The effects of the Ca2+ and 5-HT1 and 5-HT2 receptor antagonist dotarizine and of some other agonists and antagonists of different 5-HT receptor subtypes administered alone or in combination with the 5-HT uptake inhibitor fluoxetine (FLU) on nociception were studied, using a foot-pressure method (analgesy-meter testing). Dotarizine (DOT) administered at a dose of 50 mg/kg for 3 days orally significantly increased the pain threshold. Fluoxetine (FLU) administered at a dose of 10 mg/kg for 3 days also significantly increased the pain threshold. The combination of DOT and FLU abolished the analgesic effects of the two drugs. The 5-HT1A and 5-HT1B/1C receptor agonists buspirone and m-CPP decreased the pain threshold. The antagonists of 5-HT1A(NAN-190),5-HT1/5-HT2(methysergide), 5-HT2 (ritanserin), and 5-HT3 (ondansetron) receptors as well as the agonists of 5-HT2(DOI) and 5-HT3 (mCPBG) receptors increased the pain threshold. Fluoxetine at a single dose of 10 mg/kg differently influenced the effects of the 5-HT agonists and antagonists on nociception. Comparison of the effects of dotarizine with the effects of some of the agonists and antagonists of 5-HT receptor subtypes on the nociceptive and other actions suggests the possibility of a therapeutic value of dotarizine as an antimigraine drug.
Belcheva
S
S
Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Petkov
V D
VD
Konstantinova
E
E
Petkov
V V
VV
Boyanova
E
E
D000818:Animals; D001559:Benzhydryl Compounds / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005473:Fluoxetine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects*; D010879:Piperazines / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D001559:Benzhydryl Compounds; D002121:Calcium Channel Blockers; D005473:Fluoxetine; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C083946:dotarizine