Antinociceptive effect of ketanserin in mice: involvement of supraspinal 5-HT2 receptors in nociceptive transmission.
The involvement of 5-HT2 receptors in pain transmission was investigated in mice. Subcutaneous administration of the selective 5-HT2 receptor antagonist ketanserin produced dose-dependent antinociception in the hot-plate and acetic acid-induced writhing tests with ED50 values (95% confidence limit) of 1.51 (1.13-1.89) and 0.62 (0.10-1.40) mg/kg, respectively, but was without any significant effect on the tail-flick test. Pretreatment with the catecholamine depletors 6-hydroxydopamine (2.5 micrograms, i.c.v.) or alpha-methyl-p-tyrosine (200 mg/kg, s.c.), or the serotonin synthesis inhibitor p-chlorophenylalanine methylester (200 mg/kg, s.c.), resulted in a significant decrease in the antinociceptive effect of ketanserin. Likewise, intrathecal (i.t.) administration of 1 microgram/mouse of idazoxan (an alpha 2-antagonist), methysergide (mixed 5-HT1, and 5-HT2 antagonist) or ketanserin also reversed the antinociceptive effect of s.c. administered ketanserin. The results of this work indicate that 5-HT2 receptors located supraspinally may inhibit descending nociceptive neurotransmission. In addition, these studies suggest that 5-HT2 receptors located at the spinal level modulate nociception.
Department of Pharmacology, Medical School, University of Minnesota, Minneapolis 55455.
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Alhaider
D000085:Acetates; D019342:Acetic Acid; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D019329:Idazoxan; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000085:Acetates; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D004146:Dioxanes; D011985:Receptors, Serotonin; D012701:Serotonin; D007650:Ketanserin; D019342:Acetic Acid; D004298:Dopamine; D009638:Norepinephrine; D008784:Methysergide; D019329:Idazoxan