Afobazole prevents motor function impairment in mice with 6-OHDA induced Parkinsonism

Abstract

Resume. Objective. Current insufficiency in treatment of Parkinson’s disease determines the search for new pharmacological targets to achieve neuroprotection and reduce the severity of motor impairment. It is known that ligand activation of chaperone sigma-1 (SigmaR1) and inhibition of quinone reductase 2 (NQO2) cause cytoprotection. Anxiolytic drug afobazole (5-Ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole dihidrochloride) interacts with SigmaR1 and regulatory site of NQO2, inhibiting it. In vivo and in vitro experiments have demonstrated neuroprotective effect of afobazole. However, the effect of afobazole on motor deficit and motion coordination in model of Parkinson’s disease was not studied. Aim. To study the influence of afobazole on latency to fall in rotarod test in mice with induced 6-hydroxydopamine (6-OHDA) Parkinsonism. Methods. Male CD-1 (ICR) mice were tested at accelerated and constant speed rotarod. Afobazole was administered during 14 days (2.5 mg/kg, ip) at course start 30 minutes after unilateral intrastriatal injection of 5 |xg 6-OHDA. Results. Chronic administration of afobazole (2.5 mg/kg) to hemiparkinsonian mice increases their latency to fall 3.9 fold contrary to placebo treated mice in constant speed rotarod. Afobazole negates 6-OHDA in accelerating rotarod increasing latency to fall 1.6 fold as compared to placebo group. Conclusion. Afobazole prevents motor function impairment in hemiparkinsonian mice with 6-OHDA lesion in rotarod test. Observed effect of afobazole can be a result of it neuroprotective properties derived from SigmaR1 and NQO2 interaction.

Keywords

• 6-гидроксидофамин
• вращающийся стержень
• афобазол
• 6-ohda
• rotarod
• afobazole