The monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP-treated and levodopa-primed common marmosets
✍ Scribed by Ronald K.B. Pearce; Lance A. Smith; Michael J. Jackson; Tara Banerji; Jorgen Scheel-Krüger; Peter Jenner
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 431 KB
- Volume
- 17
- Category
- Article
- ISSN
- 0885-3185
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✦ Synopsis
Abstract
The common marmoset develops motor deficits after MPTP treatment and exhibits dyskinesia after chronic levodopa (L‐dopa) dosing and subsequent re‐challenge with L‐dopa and other dopaminergic agents. We report on the actions of the potent monoamine reuptake blocker brasofensine on motor disability, locomotor activity, and dyskinesia in the 1‐methyl‐4‐1, 2,3,6‐tetrahydropyridine (MPTP) ‐treated marmoset model of Parkinson's disease. Oral administration of brasofensine (0.25, 0.5, 1.0, or 2.5 mg/kg) to MPTP‐treated marmosets produced a long‐lasting, dose‐dependent increase in locomotor activity and reduction in disability scores. In addition, coadministration of the lowest dose of brasofensine (0.25 mg/kg orally) with a threshold oral dose of L‐dopa (2.5 mg/kg) caused a marked increase in locomotor activity, greater than that produced by either drug alone. In other MPTP‐treated marmosets previously primed to exhibit dyskinesia by repeated L‐dopa dosing, brasofensine effectively reversed akinesia with a naturalistic and prolonged motor response without the appearance of dyskinesia or stereotypy. This finding contrasts with the severe dyskinesia, stereotypy, and hyperkinesis produced by equivalent doses of L‐dopa. The ability of brasofensine to produce a prolonged and naturalistic antiparkinsonian response without eliciting dyskinesia after previous L‐dopa priming may relate to actions on D~1~ receptor‐linked pathways. These findings suggest that monoamine reuptake blockade may be of value in the treatment of Parkinson's disease, both early in the disease course and when L‐dopa–induced dyskinesias complicate treatment. © 2002 Movement Disorder Society