Tramadol-induced seizurogenic effect: a possible role of opioid-dependent histamine (H1) receptor activation-linked mechanism

The present study has been designed to investigate the role of opioid receptors, mast cells, and histamine receptors (H 1 subtype) in the seizurogenic effect of tramadol on pentylenetetrazole-treated mice. A single injection of pentylenetetrazole (80 mg kg −1 ) was used to elicit seizure activity in mice. Seizures were assessed in terms of the time latency of the onset of Straub-like tail, onset of jerky movements of whole body, convulsions, and death. Tramadol administration (50 mg kg −1 ) caused a marked increase in seizurogenic activity of pentylenetetrazole as measured in terms of a significant decrease in the time latency of the onset of Straub-like tail, jerky movements of whole body, convulsions, and death. Moreover, prior administration of naloxone (2 mg kg −1 ), fexofenadine (100 mg kg −1 ), cetrizine, sodium cromoglycate, and ketotifen (10 mg kg −1 ), respectively, attenuated the seizurogenic activity that tramadol exerted on pentylenetetrazole-treated mice. Therefore, it may be suggested that tramadol exerts a seizurogenic effect on mice via an H 1 receptor activation-linked pathway possibly through an opioid receptor-dependent release of histamine from the mast cells.