Evidence of the antiepileptic potential of amiloride with neuropharmacological benefits in rodent models of epilepsy and behavior.
Sodium-hydrogen exchangers (NHEs) in the brain play a key role in regulating neuronal pH and, hence, modulate bioelectric and seizure activity. In this study, we investigated the anticonvulsant effect of amiloride (a NHE inhibitor) on increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizures in mice. Further, the effect of amiloride on mood, memory, grip strength, and rotarod performance was also evaluated. The forced swimming test (FST) and spontaneous alternation behavior (SAB) models were employed to assess the effects on mood and memory, respectively. Amiloride produced a dose-dependent increase in seizure threshold in both rodent models of epilepsy. It was observed that amiloride reduced behavioral depression in the FST in mice. In addition, it resulted in memory improvement in the SAB model. Amiloride did not affect grip strength and rotarod performance, suggesting it is devoid of behavioral impairment. The results indicate the potential antiseizure activity of amiloride along with additional neurological advantages.
Ali
Atif
A
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110 062, India.aliatif@rediffmail.com
Ahmad
Farhan Jalees
FJ
Pillai
K K
KK
Vohora
Divya
D
D000584:Amiloride / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010433:Pentylenetetrazole; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D013550:Swimming; D013997:Time Factors
D000927:Anticonvulsants; D000584:Amiloride; D010433:Pentylenetetrazole