Pharmacological and toxicological evaluation of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxoide against haloperidol induced Parkinson like symptoms in animal model: In-vitro and in-vivo studies

Abstract

In Parkinson's disease (PD), degradation of dopaminergic neurons in substantia nigra causes striatal deficiency of dopamine, which results in tremors, bradykinesia with instability in posture, rigidity and shuffled gait. Prevalence of PD increases with age as from 65 to 85 years. In an attempt to devise targeted safe therapy, nanoparticles of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (MBD) (MBDN), were prepared and their acute toxicity and safety was evaluated. Thirty-six healthy albino mice were randomly divided into six groups (n = 6): normal control, diseased control, standard (levodopa/carbidopa (100/25 mg/kg) and the remaining three groups were administered 1.25, 2.5 and 5 mg/kg MBDN during 21 days study. Except control, all mice, were injected haloperidol (1 mg/ kg i.p.) 1-h prior to treatment to induce PD. Acute toxicity test showed, no effect of MBDN on lipid profile, brain, renal and liver function and histoarchitecture of kidney, liver and heart, except decreased (p < 0.05) platelet count. Behavioral studies showed significant improvement (p < 0.001) in motor function and reduction of oxidation status in a MBDN in a dose dependent manner. Thus, the study findings revealed significance of MBDN as a selective MAO-B inhibitor for the improvement of Parkinson's symptoms in animal model.