Potentiation of the antinociceptive effect of clomipramine by a 5-ht(1A) antagonist in neuropathic pain in rats.
The benefit of antidepressant treatment in human neuropathic pain is now well documented, but the effect is limited and slow to appear. It has been demonstrated that the association of a 5-HT(1A) antagonist and a serotoninergic antidepressant reduced the delay of action and increases the thymoanaleptic effect of the drug. The purpose of this work was to evaluate the combination of an antidepressant and a 5-HT(1A) antagonist in animal models of chronic neuropathic pain. We studied the antinociceptive effect of the co-administration of clomipramine and a 5-HT(1A) antagonist (WAY 100,635) in a pain test applied in normal rats and in two models of neurogenic sustained pain (mononeuropathic and diabetic rats). The results show an increase in the antinociceptive effect of acutely injected clomipramine due to WAY 100,635 in these models, which is majored when the two drugs are repeatedly injected. The 5-HT(1A) antagonist reduced the delay of onset and increased the maximal antinociceptive effect of clomipramine. These new findings argue for using the combination of an antidepressant and a 5-HT(1A) antagonist in human neuropathic pain therapy.
EPI INSERM 9904, Laboratoire de pharmacologie Médicale, Faculté de médecine, 63001 Clermont-Ferrand Cedex, France. Denis.ARDID@u-clermont1.fr
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Ardid
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Alloui
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Brousse
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Jourdan
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Picard
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Dubray
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Eschalier
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D019540:Area Under Curve; D002997:Clomipramine / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D008297:Male; D010147:Pain Measurement / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D002997:Clomipramine