Antinociception in rat by sarpogrelate, a selective 5-HT(2A) receptor antagonist, is peripheral.
The antinociceptive effect of sarpogrelate, a new selective 5-hydroxytriptamine (5-HT)(2A) receptor antagonist, in the formalin test was examined in rats. Sarpogrelate was administered intraperitoneally, locally (subcutaneously at the formalin test site) or intrathecally 10 min before formalin injection. Intraperitoneal (1-100 mg/kg) and local (0.01-1 mg) administration of sarpogrelate suppressed flinching behavior in both phases 1 (0-9 min) and 2 (10-60 min) in a dose-dependent manner. Intraperitoneal (100 mg/kg) and local (1 mg) injection 7 min after formalin injection reduced phase 2 flinches to the same degree as with the pre-treatment. Intrathecal administration (1-100 microg) showed no antinociceptive action, and facilitated phase 2 flinches at 10 microg. The plasma concentration of sarpogrelate after local administration of 1 mg was lower than after intraperitoneal administration of 10 mg/kg, although local administration produced more potent antinociception. The data imply that the antinociceptive effect of sarpogrelate results mainly from an action at peripheral sites.
Obata
H
H
Department of Anesthesiology and Reanimatology, Gunma University, School of Medicine, 3-39-22, Showa-machi, Gunma, 371-8511, Maebashi, Japan. hobata@showa.gunma-u.ac.jp
Saito
S
S
Ishizaki
K
K
Goto
F
F
D000700:Analgesics / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012018:Reflex / Q000187:drug effects; D012702:Serotonin Antagonists / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D013386:Succinates / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
D000700:Analgesics; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate