Systemic delivery of selective EP1 and EP3 receptor antagonists attenuates pentylenetetrazole-induced seizures in mice.

Systemic delivery of selective EP1 and EP3 receptor antagonists attenuates pentylenetetrazole-induced seizures in mice. Int J Physiol Pathophysiol Pharmacol. 2018;10(1):47-59 Authors: Reschke CR, Poersch AB, Masson CJ, Jesse AC, Marafiga JR, Lenz QF, Oliveira MS, Henshall DC, Mello CF Abstract Neuroinflammation plays a major role in brain excitability and may contribute to the development of epilepsy. Prostaglandin E2 (PGE2) is a direct mediator of inflammatory responses and, through EP receptors, plays an important role in neuronal excitability. Pharmacological evidence supports that centrally-administered EP1 and EP3 receptor antagonists reduced acutely evoked seizures in rats. Translation of these findings would benefit from evidence of efficacy with a more clinically relevant route of delivery and validation in another species. In the current study we investigated whether the systemic administration of EP1 and EP3 agonists and antagonists modulate pentylenetetrazole (PTZ)-induced seizures in mice. In addition, it was examined whether these compounds alter Na+, K+-ATPase activity, an enzyme responsible for the homeostatic ionic equilibrium and, consequently, for the resting membrane potential in neurons. While the systemic administration of EP1 and EP3 antagonists (ONO-8713 and ONO-AE3-240, respectively) attenuated, the respective agonists (ONO-DI-004 and ONO-AE-248) potentiated PTZ-induced seizures (all compounds injected at the ...
Source: International Journal of Physiology, Pathophysiology and Pharmacology - Category: Physiology Tags: Int J Physiol Pathophysiol Pharmacol Source Type: research