title: Biochemical and neurotransmitters changes associated with tramadol in streptozotocin-induced diabetes in rats.
abstract: The incidence of diabetes is increasing worldwide. Chronic neuropathic pain occurs in approximately 25% of diabetic patients. Tramadol, an atypical analgesic with a unique dual mechanism of action, is used in the management of painful diabetic neuropathy. It acts on monoamine transporters to inhibit the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA). The purpose of this study was to evaluate the effects of diabetes on the brain neurotransmitter alterations induced by tramadol in rats, and to study the hepatic and renal toxicities of the drug. Eighty Sprague-Dawley rats were divided randomly into two sets: the normal set and the diabetic set. Diabetes was induced in rats. Tramadol was administered orally once daily for 28 days. The levels of DA, NE, and 5-HT in cerebral cortex, thalamus/hypothalamus, midbrain, and brainstem were evaluated in rats. In addition, the renal toxicity and histopathological effects of the drug were assessed. The induction of diabetes altered neurotransmitter levels. Oral administration of tramadol significantly decreased the neurotransmitter levels. Diabetes significantly altered the effects of tramadol in all brain regions. Tramadol affected function and histology of the liver and kidney. The clinical effects of tramadol in diabetic patients should be stressed.
authors: Drug Bioavailability Laboratory, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia ; National Organization for Drug Control and Research, P.O. Box 29 Cairo, Egypt.
authors: Essam
authors: E
authors: Ezzeldin
authors: National Organization for Drug Control and Research, P.O. Box 29 Cairo, Egypt.
authors: Wafaa A H
authors: WA
authors: Souror
authors: Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al Azhar University, Cairo, Egypt.
authors: Toqa
authors: T
authors: El-Nahhas
authors: National Organization for Drug Control and Research, P.O. Box 29 Cairo, Egypt.
authors: Abdel Nasser M M
authors: AN
authors: Soudi
authors: Pharmacognosy Department, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors: Abdelaaty A
authors: AA
authors: Shahat
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013311:Streptozocin; D014147:Tramadol / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D018377:Neurotransmitter Agents; D012701:Serotonin; D014147:Tramadol; D013311:Streptozocin; D004298:Dopamine; D009638:Norepinephrine