B Vitamins Supplement Potentiates Antiparkinsonian Effect of Flunarizine: the Behavioral and Biochemical Evidences From 6-Hydroxydopamine Animal Model

Introduction: Prominent data indicate that flunarizine (flu), a calcium channel blocker, has neuroprotective effect. However, several authors have reported that the chronic use of flu can produce drug-induced Parkinsonism. Previously, we showed that B vitamins supplement (B com) has antiparkinsonian effect. In the present study, we evaluated the effect of pretreatment with flu and a combination of flu and B com on the 6-hydroxydopamine (6-OHDA) - induced Parkinsonism. Methods: 6-OHDA (4 μl, 4 μg/μl) was injected into right striatum by stereotaxic surgery. Different groups of rats received flu (5 or 10 mg/kg) or B com or a combination of them before the toxin to three weeks after that. The severity of Parkinsonism was assessed by conventional behavioral tests and also biochemical measurement of striatal dopamine level. Furthermore, malondialdehyde (MDA) concentration was measured in the serum and brain suspension. Results: Pretreatments with flu or B com significantly attenuated apomorphine- induced rotations and improved rotarod performance, but they had little effect on the 6- OHDA- induced swinging behavior. The pretreatments also reduced the decreasing effect of 6- OHDA on the striatal dopamine level. These antiparkinsonian effects were potentiated when animals were pretreated with a combination of flu and B com. In addition, B com alone or in combination with flu reduced MDA concentration especially in the brain tissue. On the other hand, flu increased MDA concentration in the serum. Conclusion: Our data show that co-administration of B com with flu potentiate largely the antiparkinsonian effect and may attenuate its adverse effects.