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• W2040706937 endingPage "1585" @default.
• W2040706937 startingPage "1577" @default.
• W2040706937 abstract "1. The treatment of Parkinson's disease relies predominantly upon dopamine replacement therapy, usually with l-dihydroxyphenylalanine (L-DOPA). However, side-effects of long-term treatment, such as L-DOPA-induced dyskinesias can be more debilitating than the disease itself. Non-dopaminergic treatment strategies might therefore be advantageous. 2. The aim of this study was to investigate the potential anti-parkinsonian efficacy of the kappa-opioid receptor agonist, enadoline, and the alpha-adrenoreceptor agonist, clonidine, both alone or in combination, in the reserpine-treated rat model of Parkinson's disease. 3. Rats were treated with reserpine (3 mg kg-1), and experiments carried out 18 h later, at which time they exhibited profound akinesia (normal animals 1251+/-228 mobile counts h-1, reserpine-treated animals 9+/-2 mobile counts h-1). Both enadoline and clonidine increased locomotion in reserpine-treated rats in a dose-dependent manner. The maximum locomotor-stimulating effect of enadoline alone was seen at a dose of 0.2 mg kg-1 (208+/-63 mobile counts h-1). The maximum effect of clonidine was seen at a dose of 2 mg kg-1 (536+/-184 mobile counts h-1). 4. Co-administration of enadoline (0.1 mg kg-1) and clonidine (0.01 - 0.1 mg kg-1) at sub-threshold doses, synergistically increased locomotion. 5. The synergistic stimulation of locomotion in the reserpine-treated rat involved activation of kappa-opioid receptors and a combination of both alpha1 and alpha2-adrenoreceptors. 6. The results presented suggest a need for further studies on the potential of stimulating kappa-opioid and/or alpha-adrenoreceptors as a therapy for Parkinson's disease. Furthermore, the studies may offer potential mechanistic explanations of the ability of alpha2-adrenergic receptor antagonist to reduce L-DOPA-induced dyskinesia in Parkinson's disease." @default.
• W2040706937 created "2016-06-24" @default.
• W2040706937 creator A5018228116 @default.
• W2040706937 creator A5044200001 @default.
• W2040706937 date "1999-12-01" @default.
• W2040706937 modified "2023-10-16" @default.
• W2040706937 title "The adrenergic receptor agonist, clonidine, potentiates the anti-parkinsonian action of the selective κ-opioid receptor agonist, enadoline, in the monoamine-depleted rat" @default.
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• W2040706937 doi "https://doi.org/10.1038/sj.bjp.0702943" @default.
• W2040706937 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1571785" @default.
• W2040706937 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10602339" @default.
• W2040706937 hasPublicationYear "1999" @default.
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