The NMDA antagonist budipine can alleviate levodopa-induced motor fluctuations

Spieker, Sybille; Löschmann, Peter‐Andreas; Klockgether, Thomas

doi:10.1002/1531-8257(199905)14:3<517::aid-mds1025>3.0.co;2-u

Cited by 18 publications

(4 citation statements)

References 22 publications

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“…In addition, the NMDA receptor antagonists, dextrorphan, dextromethorphan, amantadine (Verhagen Metman et al 1998 a, b) and budipine (Spieker et al 1999) have been found to improve L-DOPA induced motor complications in parkinsonian patients. Furthermore, the NMDA receptor antagonist Co 101244, which is selective for the NR1\NR2B receptor subtype, displays antidyskinetic effects without compromising the antiparkinsonian actions of L-DOPA in MPTP-treated monkeys (Blanchet et al 1999).…”

Section: Parkinson's Diseasementioning

confidence: 99%

NMDA receptors in the basal ganglia

Ravenscroft

Brotchie

2000

Journal of Anatomy

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The basal ganglia consist of several interconnected nuclei located in the telecephalon, diencephalon and mesencephalon that are involved in a variety of motor and non-motor behavioural functions. Glutamate receptors play a major role in neurotransmission within the basal ganglia and are present in all nuclei of the basal ganglia. This review focuses on the contribution of the NMDA class of glutamatergic receptors to various movement disorders whose primary pathology lies within the basal ganglia and discusses how pharmacological manipulation of such receptors may be therapeutically useful.

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Section: Parkinson's Diseasementioning

confidence: 99%

NMDA receptors in the basal ganglia

Ravenscroft

Brotchie

2000

Journal of Anatomy

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“…Moreover, systemic administration of NMDA receptor antagonists prevents or reduces LID without affecting the antiparkinsonian response to L ‐dopa in MPTP parkinsonian monkeys 25–27. In the clinical realm, amantadine, budipine, and memantine, all drugs with significant potency as NMDA receptor antagonists, can improve LID in PD patients 28–30. Taken together, these studies suggest that heightened glutamate receptor activity could play a role in the pathophysiology of LID, and interventions that reduce glutamatergic activity hold promise for the treatment of LID 15, 16, 31, 32…”

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confidence: 99%

Effect of kynurenine 3‐hydroxylase inhibition on the dyskinetic and antiparkinsonian responses to levodopa in parkinsonian monkeys

et al. 2005

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Homeostatic interactions between dopamine and glutamate are central to the normal physiology of the basal ganglia. This relationship is altered in Parkinsonism and in levodopa-induced dyskinesias (LID), resulting in an upregulation of corticostriatal glutamatergic function. Kynurenic acid (KYNA), a tryptophan metabolite with antagonist activity at ionotropic glutamate receptors and the capability to inhibit glutamate release presynaptically, might therefore be of therapeutic value in LID. To evaluate this hypothesis, we used a pharmacological tool, the kynurenine 3-hydroxylase inhibitor Ro 61-8048, which raises KYNA levels acutely. Ro 61-8048 was tested in MPTP cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias after each dose of levodopa. Serum and CSF concentrations of KYNA and its precursor kynurenine increased dose-dependently after Ro 61-8048 administration, alone or in combination with levodopa. Coadministration of Ro 61-8048 with levodopa produced a moderate but significant reduction in the severity of dyskinesias while maintaining the motor benefit. These results suggest that elevation of KYNA levels through inhibition of kynurenine 3-hydroxylase constitutes a promising novel approach for managing LID in Parkinson's disease.

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“…[3][4][5][6][7] Eltze 8 provides a review. Previous clinical trials [9][10][11][12] have demonstrated the therapeutic efficacy of budipine on motor symptoms in subjects with PD who receive an insufficient antiparkinsonian drug regimen. Przuntek and Mü ller 13 provide a review.…”

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confidence: 99%