Raloxifene potentiates the effect of fluoxetine against maximal electroshock induced seizures in mice

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Faheem Hyder PottooGhulam Md Ashraf

Abstract

The evidence to guide clinicians regarding rationale polytherapy with current antiepileptic drugs (AEDs) is lacking, and current practice recommendations are largely empirical.  The excessive drug loading with combinatorial therapies of existing AEDs are associated with escalated neurotoxicity, and that emergence of pharmacoresistant seizures couldn't be averted. In pursuit of judicious selection of novel AEDs in combinatorial therapies with mechanism based evidences, standardized dose of raloxifene, fluoxetine, bromocriptine and their low dose combinations, were experimentally tested for their impact on maximal electroshock (MES) induced tonic hind limb extension (THLE) in mice. Hippocampal neuropeptide Y (NPY) levels, oxidative stress and histopathological studies were undertaken. The results suggest the potentiating effect of 4 mg/kg raloxifene on 14 mg/kg fluoxetine against MES induced THLE, as otherwise monotherapy with 4 mg/kg raloxifene was unable to produce an effect. The results also depicted better efficacy than carbamazepine (20 mg/kg), standard AED. Most profoundly, MES-induced significant (P < 0.001) reduction in hippocampal NPY levels, that were escalated insignificantly with the duo-drug combination, suggesting s...Continue Reading

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Citations

May 29, 2020·The European Journal of Neuroscience·Abdallah Mohammad IbrahimJ B Senthil Kumar
Apr 4, 2021·International Journal of Molecular Sciences·Kinga K Borowicz-Reutt
Oct 30, 2021·Journal of Neuroscience Research·Enes AkyuzYam Nath Paudel
Sep 4, 2021·CNS & Neurological Disorders Drug Targets·Rishabh VermaMohamad Taleuzzaman

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