Abstract

PREVENTION OF EPILEPSY BY LOW-DOSE ARTESUNATE + ESOMEPRAZOLE-FUROSEMIDE SEQUENTIAL THERAPY.

*S. E. Oriaifo, N. Oriaifo, J. Eigbefo, E. Okogbenin and C. Iruolagbe

ABSTRACT

Very recent findings indicate an important neuromodulatory role for astrocytes in altering neural circuit activity and behaviour. Artesunate, esomeprazole and furosemide are now verified agents that modulate noxious agents-induced hazardous orchestra via ATP- P2X7R-P2YI-NLRP3-A2AR signalling in astrocytes. Their mechanisms of action converge on down-regulating hyperglutamatergic excitotoxicity-and caspase-I-induced pyroptosis. They are therfore in a position to down-regulate inflammatory-related oxidative stress implicated in the mechanisms of chronic CNS diseases such as type 2 diabetes-induced complications, epilepsy and Alzheimer’s disease. Importantly, these agents, which also exhibit anti-malarial activities, may become significant alternatives to present AEDs which are associated with short-comings such as drug resistance, cognitive decline, oxidative stress and even metabolic syndrome. In the present study, the effect of intermittent low-dose artesunate + esomeprazole and furosemide sequential therapy was investigated for their anti-epileptic effects. In children, intermittent use of these agents over a period of 4 months significantly (P< 0.05) abrogated seizure recurrence in six patients with epilepsy and status epilepticus studied. Episodes of fever were also reduced in those who were placed on the sequential combination therapy. The drugs deserve careful attention in our locality where malaria, other infections and birth injuries have co-operated to maintain, at least, a sustained prevalence rate of epilepsy and related illnesses.

Keywords: Artesunate, Esomeprazole, Furosemide, Excitotoxicity, Seizures, Attenuation.