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Noradrenergic drugs for levodopa-induced dyskinesia.
Clin Neuropharmacol. 2003 Nov-Dec; 26(6):299-305.CN

Abstract

Dyskinesia frequently mars the long-term therapeutic response to levodopa (LD) in Parkinson's disease (PD). New treatment strategies for levodopa-induced dyskinesia (LID) currently being investigated include some that target the nondopaminergic pathways. Indeed, LID in parkinsonism can be modulated by drugs acting on different neurotransmitters including glutamate, gamma-aminobutyric acid, noradrenaline, acetylcholine, serotonin, adenosine, and cholecystokinin. In many cases, the possibility of using specific compounds to counteract LID was raised by the previously shown efficacy of such compounds in the treatment of other types of dyskinesia. More data are now available on drugs that act on the noradrenergic system. Two studies have recently shown how the alpha-2 adrenoreceptor antagonist idazoxan can significantly reduce LID in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of parkinsonism and in patients with advanced PD. The experimental paper, which studied the antagonistic action of idazoxan on dyskinesia induced by both LD and apomorphine in marmosets with MPTP-induced parkinsonism, showed that the pharmacologic mechanisms underlying LID and apomorphine-induced dyskinesia in PD are probably distinct. LD, although not apomorphine-induced, dyskinesia was found to be influenced by adrenoreceptor antagonists. Indeed, the action of alpha-2 adrenoreceptor antagonists may involve the blockade of the action of noradrenaline synthesized from LD. The hypothesis is that because dopamine agonists are not metabolized to noradrenaline, alpha-2 adrenoreceptor antagonists do not reduce dyskinesia produced by such agents. This finding is particularly relevant in planning clinical studies in which LD or dopamine agonist challenges are used to assess the potential antidyskinetic properties of new drugs. The clinical study assessed the effects of idazoxan on LID in 18 patients with advanced PD: An improvement in LID, without the reappearance of parkinsonian symptoms, was observed. The practical outcome of this research is that, although the mechanisms underlying the manifestations and the priming process for dyskinesia have yet to be fully elucidated, a nondopaminergic approach to therapy may provide an effective way of preventing, or at least limiting, the expression of involuntary movements in PD.

Authors+Show Affiliations

Department of Neurological Science. University La Sapienza, viale dell'Università 30, I-00185 Rome, Italy. carlo.colosimo@uniroma1.itNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

14646609

Citation

Colosimo, Carlo, and Alessandra Craus. "Noradrenergic Drugs for Levodopa-induced Dyskinesia." Clinical Neuropharmacology, vol. 26, no. 6, 2003, pp. 299-305.
Colosimo C, Craus A. Noradrenergic drugs for levodopa-induced dyskinesia. Clin Neuropharmacol. 2003;26(6):299-305.
Colosimo, C., & Craus, A. (2003). Noradrenergic drugs for levodopa-induced dyskinesia. Clinical Neuropharmacology, 26(6), 299-305.
Colosimo C, Craus A. Noradrenergic Drugs for Levodopa-induced Dyskinesia. Clin Neuropharmacol. 2003 Nov-Dec;26(6):299-305. PubMed PMID: 14646609.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Noradrenergic drugs for levodopa-induced dyskinesia. AU - Colosimo,Carlo, AU - Craus,Alessandra, PY - 2003/12/4/pubmed PY - 2004/2/10/medline PY - 2003/12/4/entrez SP - 299 EP - 305 JF - Clinical neuropharmacology JO - Clin Neuropharmacol VL - 26 IS - 6 N2 - Dyskinesia frequently mars the long-term therapeutic response to levodopa (LD) in Parkinson's disease (PD). New treatment strategies for levodopa-induced dyskinesia (LID) currently being investigated include some that target the nondopaminergic pathways. Indeed, LID in parkinsonism can be modulated by drugs acting on different neurotransmitters including glutamate, gamma-aminobutyric acid, noradrenaline, acetylcholine, serotonin, adenosine, and cholecystokinin. In many cases, the possibility of using specific compounds to counteract LID was raised by the previously shown efficacy of such compounds in the treatment of other types of dyskinesia. More data are now available on drugs that act on the noradrenergic system. Two studies have recently shown how the alpha-2 adrenoreceptor antagonist idazoxan can significantly reduce LID in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of parkinsonism and in patients with advanced PD. The experimental paper, which studied the antagonistic action of idazoxan on dyskinesia induced by both LD and apomorphine in marmosets with MPTP-induced parkinsonism, showed that the pharmacologic mechanisms underlying LID and apomorphine-induced dyskinesia in PD are probably distinct. LD, although not apomorphine-induced, dyskinesia was found to be influenced by adrenoreceptor antagonists. Indeed, the action of alpha-2 adrenoreceptor antagonists may involve the blockade of the action of noradrenaline synthesized from LD. The hypothesis is that because dopamine agonists are not metabolized to noradrenaline, alpha-2 adrenoreceptor antagonists do not reduce dyskinesia produced by such agents. This finding is particularly relevant in planning clinical studies in which LD or dopamine agonist challenges are used to assess the potential antidyskinetic properties of new drugs. The clinical study assessed the effects of idazoxan on LID in 18 patients with advanced PD: An improvement in LID, without the reappearance of parkinsonian symptoms, was observed. The practical outcome of this research is that, although the mechanisms underlying the manifestations and the priming process for dyskinesia have yet to be fully elucidated, a nondopaminergic approach to therapy may provide an effective way of preventing, or at least limiting, the expression of involuntary movements in PD. SN - 0362-5664 UR - https://www.unboundmedicine.com/medline/citation/14646609/Noradrenergic_drugs_for_levodopa_induced_dyskinesia_ L2 - https://doi.org/10.1097/00002826-200311000-00008 DB - PRIME DP - Unbound Medicine ER -