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The monoamine reuptake inhibitor BTS 74 398 fails to evoke established dyskinesia but does not synergise with levodopa in MPTP‐treated primates
Author(s) -
Hansard Matthew J.,
Smith Lance A.,
Jackson Michael J.,
Cheetham Sharon C.,
Jenner Peter
Publication year - 2004
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.10596
Subject(s) - dyskinesia , mptp , levodopa , reuptake inhibitor , reuptake , monoamine neurotransmitter , medicine , dopamine , parkinson's disease , parkinsonism , pharmacology , psychology , anesthesia , endocrinology , serotonin , dopaminergic , disease , receptor
Long‐term treatment of Parkinson's disease (PD) with levodopa ( L ‐dopa) induces dyskinesia that, once established, is provoked by each dose of L ‐dopa or a dopamine (DA) agonist. In contrast, monoamine reuptake inhibitors may reverse motor deficits in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated primates without provoking established involuntary movements. We now examine whether the potent monoamine reuptake blocker BTS 74 398 induces established dyskinesia in MPTP‐treated common marmosets primed previously with L ‐dopa and whether co‐administration of BTS 74 398 with L ‐dopa potentiates motor behaviour and dyskinesia induced by acute L ‐dopa treatment. Administration of BTS 74 398 (2.5, 5.0, or 10.0 mg/kg, p.o.) in MPTP‐treated common marmosets increased locomotor activity and reduced motor disability in a dose‐related manner but did not provoke involuntary movements. BTS 74 398 (2.5, 5.0, or 10.0 mg/kg p.o.) co‐administered with a threshold dose of L ‐dopa (2.5 mg/kg p.o.) did not evoke a motor response or induce dyskinesia. Similarly, concomitant administration of BTS 74 398 (5.0 mg/kg p.o.) with a submaximal L ‐dopa dose (12.5 mg/kg p.o.) did not potentiate the motor response produced by L ‐dopa alone and there was no alteration in the dyskinesia provoked by L ‐dopa challenge. BTS 74 398 reverses motor abnormalities in MPTP‐treated marmosets without evoking established dyskinesia but no additive improvement occurs when administered in combination with L ‐dopa. The lack of synergy with L ‐dopa may suggest different sites of drug action. © 2003 Movement Disorder Society