• A M Peiró, L Climent, P Zapater, A Horga, and J F Horga.
• Alicante Clinical Trials Unit, Instituto de Bioingeniería, Miguel Hernández University, Campus de San Juan, Ctra, Alicante-Valencia, Km 87 Apdo 18, 03550 San Juan de Alicante, Alicante, Spain. peiro ana@gva.es
• Pharmacol. Res. 2011 Jul 1; 64 (1): 80-4.

AbstractHow can we treat patients with reduced morphine doses without loosing the pain killing effect or morphine antinociceptive effects (MAE)? To address this question, we hypothesized that serotonin (5-HT2) receptor antagonism could enhance MAE mediated by kappa-opioid receptors. We pretreated mice with ketanserin, a 5-HT2 receptor antagonist, and measured the morphine dose required to observe analgesia. The morphine dose effective in 50% of animals (ED(50)) was reduced from 4.7 to 1.3mg/kg, and the morphine dose effective in 100% of animals (ED(max)) from 13.7 to 2.5mg/kg. Ketanserin has a similar enhancer effect when morphine, which has a dual role via mu and kappa receptors, was substituted by the antinociceptive spiradoline, a selective κ-opioid agonist. At a morphine dose of 3.5mg/kg, 30% of the mice showed antinociceptive behaviour, rising to 100% when ketanserin was co-administered and then reduced to 20% in the presence of nor-binaltorphimine, a kappa-opioid receptor antagonist. Our data strongly suggests a serotonergic inhibition of the kappa-opioid component of MAE and the possibility that this serotonergic inhibition could be reversed through 5-HT2 receptor antagonism.Copyright © 2011 Elsevier Ltd. All rights reserved.

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