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The monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP-treated and levodopa-primed common marmosets.
Mov Disord. 2002 Sep; 17(5):877-86.MD

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.

Authors+Show Affiliations

Division of Pharmacology & Therapeutics, Guy's, King's and St. Thomas' School of Biomedical Sciences, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12360536

Citation

Pearce, Ronald K B., et al. "The Monoamine Reuptake Blocker Brasofensine Reverses Akinesia Without Dyskinesia in MPTP-treated and Levodopa-primed Common Marmosets." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 17, no. 5, 2002, pp. 877-86.
Pearce RK, Smith LA, Jackson MJ, et al. The monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP-treated and levodopa-primed common marmosets. Mov Disord. 2002;17(5):877-86.
Pearce, R. K., Smith, L. A., Jackson, M. J., Banerji, T., Scheel-Krüger, J., & Jenner, P. (2002). The monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP-treated and levodopa-primed common marmosets. Movement Disorders : Official Journal of the Movement Disorder Society, 17(5), 877-86.
Pearce RK, et al. The Monoamine Reuptake Blocker Brasofensine Reverses Akinesia Without Dyskinesia in MPTP-treated and Levodopa-primed Common Marmosets. Mov Disord. 2002;17(5):877-86. PubMed PMID: 12360536.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The monoamine reuptake blocker brasofensine reverses akinesia without dyskinesia in MPTP-treated and levodopa-primed common marmosets. AU - Pearce,Ronald K B, AU - Smith,Lance A, AU - Jackson,Michael J, AU - Banerji,Tara, AU - Scheel-Krüger,Jorgen, AU - Jenner,Peter, PY - 2002/10/3/pubmed PY - 2003/1/9/medline PY - 2002/10/3/entrez SP - 877 EP - 86 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 17 IS - 5 N2 - 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. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/12360536/The_monoamine_reuptake_blocker_brasofensine_reverses_akinesia_without_dyskinesia_in_MPTP_treated_and_levodopa_primed_common_marmosets_ L2 - https://doi.org/10.1002/mds.10238 DB - PRIME DP - Unbound Medicine ER -