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.
Rehni
Ashish K
AK
Chitkara College of Pharmacy, Chandigarh-Patiala National Highway, Rajpura, 140401, Patiala, Punjab, India. ashishkrehni@yahoo.co.in
Singh
Thakur Gurjeet
TG
Singh
Nirmal
N
Arora
Sandeep
S
D000701:Analgesics, Opioid / Q000633:toxicity*; D000818:Animals; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D011969:Receptors, Histamine H1 / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D014147:Tramadol / Q000633:toxicity*
D000701:Analgesics, Opioid; D039563:Histamine H1 Antagonists, Non-Sedating; D011969:Receptors, Histamine H1; D014147:Tramadol