Involvement of the nitric oxide pathway in the anticonvulsant effect of tramadol on pentylenetetrazole-induced seizures in mice.
In the present study, the effects of tramadol on pentylenetetrazole (PTZ)-induced seizures and involvement of nitric oxide (NO) were assessed in mice. To determine the threshold for clonic seizures, PTZ was administered intravenously. Tramadol was administered intraperitoneally (0.5-50mg/kg) 30 minutes prior to induction of seizures. The effects of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5, 1, 5, and 10mg/kg), the nitric oxide precursor L-arginine (10, 30, and 60 mg/kg), and the nonspecific opioid receptor antagonist naloxone (0.1, 0.5, 1, and 5mg/kg) on the anticonvulsant effect of tramadol were investigated. Administration of tramadol (1mg/kg) increased the threshold for seizures induced with PTZ in a monophasic, dose-independent, and time-dependent manner. Acute administration of L-NAME (5 and 10mg/kg) inhibited the anticonvulsant effect of tramadol (1mg/kg), whereas L-arginine, in the noneffective dose range (30 and 60 mg/kg), potentiated the seizure threshold when co-administered with a subeffective dose of tramadol (0.5mg/kg). Naloxone partially and dose-independently antagonized the anticonvulsant effect of tramadol (1mg/kg). These results indicate that the anticonvulsant effect of tramadol is mediated by the nitric oxide pathway and also by classic opioid receptors.
Lesani
Ali
A
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Javadi-Paydar
Mehrak
M
Khodadad
Tina Kabiri
TK
Asghari-Roodsari
Alaleh
A
Shirkhodaei
Mahyar
M
Norouzi
Abbas
A
Dehpour
Ahmad Reza
AR
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000009:adverse effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014147:Tramadol / Q000627:therapeutic use*
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D009270:Naloxone; D014147:Tramadol; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole