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Involvement of serotonin mechanisms in the antinociceptive effect of S(+)‐ketoprofen
Author(s) -
DíazReval Ma. Irene,
VenturaMartínez Rosa,
DécigaCampos Myrna,
Terrón José A.,
Cabré Francesc,
LópezMuñoz Francisco J.
Publication year - 2002
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10147
Subject(s) - serotonin , 5 ht receptor , pharmacology , tropisetron , antagonist , nociception , chemistry , receptor antagonist , receptor , ketoprofen , methysergide , medicine , biochemistry
Serotonin (5‐hydroxytryptamine; 5‐HT) plays a role in the modulation and processing of pain and evidence has been provided that some nonsteroidal anti‐inflammatory drugs (NSAIDs) act, at least in part, through this system. The present study was designed to investigate the possible participation of 5‐HT 1 , 5‐HT 2 , 5‐HT 3 , and 5‐HT 7 receptor subtypes in the antinociceptive effect of S(+)‐ketoprofen (S‐KP) at spinal and supraspinal level using the “pain induced functional impairment model in rat” (PIFIR model). S‐KP was administered orally (p.o.) and antagonist drugs for 5‐HT receptors (5‐HT 1 /5‐HT 2 , and 5‐HT 3 ) were administered intrathecally (i.t.) or intracerebroventricularly (i.c.v.) 15 min before S‐KP. S‐KP (3.4 mg/kg p.o.) produced a significant antinociceptive effect in this model. Pre‐treatment with the 5‐HT 1 /5‐HT 2 /5‐HT 7 receptor antagonist, methiothepin (1.5 μg, i.c.v.), significantly reversed the antinociceptive effect of S‐KP. In contrast, no significant differences were observed following i.t. administration of methiothepin. Pre‐treatment i.t., but not i.c.v., with the 5‐HT 3 /5‐HT 4 receptor antagonist, tropisetron (0.9 μg), on the other hand, significantly reversed S‐KP‐induced antinociception. These results indicate that serotonin mechanisms are involved in the antinociceptive effect of S‐KP. 5‐HT 1 /5‐HT 2 /5‐HT 7 receptors participate at the supraspinal level and 5‐HT 3 /5‐HT 4 receptors participate at spinal level. Drug Dev. Res. 57:187–192, 2002. © 2003 Wiley‐Liss, Inc.