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The Synergistic Effect of Raloxifene, Fluoxetine, and Bromocriptine Protects Against Pilocarpine-Induced Status Epilepticus and Temporal Lobe Epilepsy

dc.contributor.authorPottoo F.H.
dc.contributor.authorTabassum N.
dc.contributor.authorJaved M.N.
dc.contributor.authorNigar S.
dc.contributor.authorRasheed R.
dc.contributor.authorKhan A.
dc.contributor.authorBarkat M.A.
dc.contributor.authorAlam M.S.
dc.contributor.authorMaqbool A.
dc.contributor.authorAnsari M.A.
dc.contributor.authorBarreto G.E.
dc.contributor.authorAshraf G.M.
dc.date.accessioned2020-09-02T22:25:55Z
dc.date.available2020-09-02T22:25:55Z
dc.date.issued2019
dc.identifier10.1007/s12035-018-1121-x
dc.identifier.citation56, 2, 1233-1247
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5838
dc.descriptionThe present antiepileptic drugs pose several problems in the management of seizures owing to their meager neuroprotective potential, adverse effects on bone, detrimental effects on cognitive function, chronic toxicity, drug interactions, side effects including aggression, agitation, and irritability and sometimes exacerbation of seizures. We followed up progressive preclinical investigation in mice against pilocarpine (PILO)-induced status epilepticus (SE) and temporal lobe epilepsy (TLE). To determine the response of raloxifene (RF) (4 and 8 mg/kg), fluoxetine (FT) (14 and 22 mg/kg), bromocriptine (BC) (6 and 10 mg/kg), and their low-dose combinations, oral treatment was scheduled for 28 days followed by PILO (300 mg/kg, i.p). The response was stalked for intensive behavioral monitoring of convulsions, hippocampal neuropeptide Y (NPY), and oxidative stress discernment along with histomorphological studies. The resultant data confirmed the therapeutic potential of triple drug combination of raloxifene (4 mg/kg) with fluoxetine (14 mg/kg) and bromocriptine (6 mg/kg) compared to monotherapy with raloxifene (4 mg/kg), and bromocriptine (6 mg/kg) as otherwise monotherapy with fluoxetine (14 mg/kg) was ineffective to suppress convulsions; an effect better than sodium valproate (300 mg/kg), a standard AED, was validated. Most profoundly, PILO-induced compensatory increases in hippocampal NPY levels (20.01%), which was escalated (100%) with the triple drug combination. The same pattern of results was superseded for oxidative stress indices and neuronal damage. The results for the first time demonstrate the propitious role of triple drug combination in the management of SE and TLE. Therapeutically, this enhancing profile of drugs fosters a safer and more effective drug-combination regimen. [Figure not available: see fulltext.]. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
dc.language.isoen
dc.publisherHumana Press Inc.
dc.subjectDopamine
dc.subjectEpilepsy
dc.subjectNeurodegeneration
dc.subjectNeuropeptide Y
dc.subjectSerotonin
dc.subjectStatus epilepticus
dc.subjectbromocriptine mesilate
dc.subjectdiazepam
dc.subjectfluoxetine
dc.subjectneuropeptide Y
dc.subjectpilocarpine
dc.subjectraloxifene
dc.subjectvalproic acid
dc.subjectanticonvulsive agent
dc.subjectbromocriptine
dc.subjectfluoxetine
dc.subjectpilocarpine
dc.subjectraloxifene
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectanticonvulsant activity
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectconvulsion
dc.subjectdrug efficacy
dc.subjectdrug megadose
dc.subjectdrug potentiation
dc.subjectdrug safety
dc.subjectepileptic state
dc.subjectfemale
dc.subjectfollow up
dc.subjecthistopathology
dc.subjectlow drug dose
dc.subjectmale
dc.subjectmonotherapy
dc.subjectmouse
dc.subjectnerve cell lesion
dc.subjectneuroprotection
dc.subjectnonhuman
dc.subjectoxidative stress
dc.subjectpilocarpine-induced seizure
dc.subjecttemporal lobe epilepsy
dc.subjecttreatment response
dc.subjectanimal
dc.subjectchemically induced
dc.subjectcombination drug therapy
dc.subjectdisease model
dc.subjectdrug effect
dc.subjectepileptic state
dc.subjecthippocampus
dc.subjectmetabolism
dc.subjectnerve cell
dc.subjecttemporal lobe epilepsy
dc.subjectAnimals
dc.subjectAnticonvulsants
dc.subjectBromocriptine
dc.subjectDisease Models, Animal
dc.subjectDrug Synergism
dc.subjectDrug Therapy, Combination
dc.subjectEpilepsy, Temporal Lobe
dc.subjectFemale
dc.subjectFluoxetine
dc.subjectHippocampus
dc.subjectMale
dc.subjectMice
dc.subjectNeurons
dc.subjectOxidative Stress
dc.subjectPilocarpine
dc.subjectRaloxifene Hydrochloride
dc.subjectStatus Epilepticus
dc.titleThe Synergistic Effect of Raloxifene, Fluoxetine, and Bromocriptine Protects Against Pilocarpine-Induced Status Epilepticus and Temporal Lobe Epilepsy
dc.typeArticle


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