α2- and β2-Adrenoreceptor-Mediated Efficacy of the Atypical Antidepressant Agomelatine Combined With Gabapentin to Suppress Allodynia in Neuropathic Rats With Ligated Infraorbital or Sciatic Nerve
| Autor: | Matthieu Poitevin, Eric Dabala, Cecilia Gabriel, Sylvie Bourgoin, Hugo Payan, Michel Hamon, Saïd M'Dahoma, Elisabeth Mocaer |
|---|---|
| Přispěvatelé: | Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherches Internationales Servier [Suresnes] (IRIS), Neuropsychopharmacologie moléculaire, cellulaire et fonctionnelle, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gabapentin RS-127445 [SDV]Life Sciences [q-bio] infraorbital nerve sciatic nerve Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Agomelatine Serotonin receptor antagonist Pharmacology (medical) Melatonin receptor agonist chronic constriction injury ComputingMilieux_MISCELLANEOUS business.industry lcsh:RM1-950 3. Good health 030104 developmental biology Allodynia lcsh:Therapeutics. Pharmacology chemistry Neuropathic pain medicine.symptom neuropathic rats business Idazoxan agomelatine 030217 neurology & neurosurgery medicine.drug mechanical allodynia |
| Zdroj: | Frontiers in Pharmacology Frontiers in Pharmacology, Frontiers, 2018, 9, ⟨10.3389/fphar.2018.00587⟩ Frontiers in Pharmacology, Vol 9 (2018) |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2018.00587⟩ |
| Popis: | Previous data showed that neuropathic pain induced by mechanical lesion of peripheral nerves has specific characteristics and responds differently to alleviating drugs at cephalic versus extracephalic level. This is especially true for tricyclic antidepressants currently used for alleviating neuropathic pain in humans which are less effective against cephalic neuropathic pain. Whether this also applies to the antidepressant agomelatine, with its unique pharmacological properties as MT1/MT2 melatonin receptor agonist and 5-HT2B/5-HT2C serotonin receptor antagonist, has been investigated in two rat models of neuropathic pain. Acute treatments were performed 2 weeks after unilateral chronic constriction (ligation) injury to the sciatic nerve (CCI-SN) or the infraorbital nerve (CCI-ION), when maximal mechanical allodynia had developed in ipsilateral hindpaw or vibrissal pad, respectively, in Sprague-Dawley male rats. Although agomelatine (45 mg/kg i.p.) alone was inactive, co-treatment with gabapentin, at an essentially ineffective dose (50 mg/kg i.p.) on its own, produced marked anti-allodynic effects, especially in CCI-ION rats. In both CCI-SN and CCI-ION models, suppression of mechanical allodynia by 'agomelatine + gabapentin' could be partially mimicked by the combination of 5-HT2C antagonist (SB 242084) + gabapentin, but not by melatonin or 5-HT2B antagonist (RS 127445, LY 266097), alone or combined with gabapentin. In contrast, pretreatment by idazoxan, propranolol or the β2 antagonist ICI 118551 markedly inhibited the anti-allodynic effect of 'agomelatine + gabapentin' in both CCI-SN and CCI-ION rats, whereas pretreatment by the MT1/MT2 receptor antagonist S22153 was inactive. Altogether these data indicate that 'agomelatine + gabapentin' is a potent anti-allodynic combination at both cephalic and extra-cephalic levels, whose action implicates α2- and β2-adrenoreceptor-mediated noradrenergic neurotransmission. |
| Databáze: | OpenAIRE |
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