title: Effect of subacute agomelatine treatment on painful diabetic neuropathy: involvement of catecholaminergic mechanisms.
abstract: In this study, we investigated the effects of subacute agomelatine (40 and 80 mg/kg) administration on chronic hyperglycemia, metabolic parameters, and pain perception in streptozotocin-induced diabetic rats. Fasting blood glucose measurements and oral glucose tolerance tests were performed to evaluate the effect of agomelatine on glycemia, while metabolic parameters were monitored using metabolic cages. Potential effect of agomelatine on diabetes-induced mechanical and thermal allodynia was evaluated using dynamic plantar aesthesiometer and warm plate (38 °C) tests, respectively. Additionally, influence of agomelatine on hyperalgesia occurring in connection with diabetic neuropathy was examined using the Randall-Selitto (mechanical nociceptive stimulus), Hargreaves (thermal nociceptive stimulus), and cold plate (4 °C, thermal nociceptive stimulus) tests. Obtained data indicated that, in diabetic rats, agomelatine significantly improved hyperalgesia and allodynia responses, without no effect on hyperglycemia or the associated polydipsia, polyuria, and hyperphagia. Therapeutic potential of agomelatine on neuropathic pain was suppressed with α-methyl-para-tyrosine methyl ester (an inhibitor of catecholamine synthesis), phentolamine (a nonselective α-adrenoceptor antagonist), and propranolol (a nonselective β-adrenoceptor antagonist) administrations. However, p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis) pretreatment could not be achieved to reverse these antihyperalgesic and antiallodynic effects. These results suggest that the curative effect of agomelatine on neuropathic pain is mediated through rising synaptic catecholamine levels as well as through interactions with both α- and β-adrenoceptors. To our knowledge, this is the first study to show findings that indicate catecholaminergic system mediated antihyperalgesic and antiallodynic effects of agomelatine.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey.
authors.forename: Taliha H
authors.initials: TH
authors.lastname: Aydın
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey.
authors.forename: Özgür D
authors.initials: ÖD
authors.lastname: Can
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey.
authors.forename: Ümide
authors.initials: Ü
authors.lastname: Demir Özkay
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskişehir, Turkey.
authors.forename: Nazlı
authors.initials: N
authors.lastname: Turan
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010134:Fenclonine / Q000031:analogs & derivatives / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D008781:Methyltyrosines / Q000494:pharmacology; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D001786:Blood Glucose; D002395:Catecholamines; D010134:Fenclonine; D008781:Methyltyrosines; D010646:Phentolamine; D011433:Propranolol; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013311:Streptozocin; C084711:agomelatine; D009281:Naphthalenes; C020261:4-chlorophenylalanine methyl ester; C022260:alpha-methyltyrosine methyl ester
keywords: 
  Diabetes mellitus
  ; adrenoceptor; agomelatine; allodynia; hyperalgesia; neuropathy