National Institutes of Health
Washington, DC | United States
Main Specialties: Psychiatry
Additional Specialties: Psychiatry, Neurology
Primary Affiliation: National Institutes of Health - Washington, DC , United States
14PubMed Central Citations
J Affect Disord 2017 11 22;222:126-132. Epub 2017 Jun 22.
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201-1549, United States; Rocky Mountain MIRECC, Denver, CO 80220, United States; VISN 5 MIRECC, Baltimore, MD 21201 United States. Electronic address:
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Mov Disord. 2006 Sep; 21(9): 1380-3
Reported benefits of various glutamatergic receptor antagonists in Parkinson's disease (PD) prompted an evaluation of the antidyskinetic effect of a putative glutamate release inhibitor in 15 moderately advanced patients. In a 3-week, double-blind, proof-of-concept study, riluzole (200 mg/day) failed to alter parkinsonian or levodopa-induced motor complication severity. Opposing effects of a generalized inhibition of glutamate-mediated synaptic transmission may limit the usefulness of this approach to treat PD. © 2006 Movement Disorder Society
Mov Disord. 2005 Aug;20(8):932-6
Abstract Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5-HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5-HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3-week, double-blind, placebo-controlled, proof-of-concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa-induced dyskinesias and prolonged its antiparkinsonian response (P < or = 0.05). Under the conditions of this study, our findings suggest that 5-HT1A receptor stimulation in levodopa-treated parkinsonian patients can modulate striatal dopaminergic function and that 5-HT1A agonists may be useful as levodopa adjuvants in the treatment of PD. Copyright 2005 Movement Disorder Society PMID: 15791634 [PubMed - indexed for MEDLINE]
Mov Disord. 2004 Oct;19(10):1183-6.
Dopamine reuptake blockers, by enhancing and stabilizing intrasynaptic transmitter levels, could help palliate motor dysfunction in Parkinson's disease. This randomized, double-blind, placebo-controlled study compared the acute effects of the monoamine uptake inhibitor NS 2330 to those of placebo in 9 relatively advanced parkinsonian patients. At the dose administered, no change in parkinsonian scores was found when NS 2330 was given alone or with levodopa. Moreover, NS 2330 coadministration did not appear to alter dyskinesia severity or the duration of the antiparkinsonian response to levodopa. The drug was well tolerated. Under the conditions of this study, the present results failed to support the usefulness of dopamine reuptake inhibition in the treatment of advanced Parkinson's disease. © 2004 Movement Disorder Society
Neurology 2003 Dec;61(11 Suppl 6):S107-11
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA.
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Neurology. 2003 Aug 12;61(3):293-6
Abstract BACKGROUND: Observations in animal models suggest that A(2A) antagonists confer benefit by modulating dopaminergic effects on the striatal dysfunction associated with motor disability. This double-blind, placebo-controlled, proof-of-principle study evaluated the pathogenic contribution and therapeutic potential of adenosine A(2A) receptor-mediated mechanisms in Parkinson disease (PD) and levodopa-induced motor complications. METHODS: Fifteen patients with moderate to advanced PD consented to participate. All were randomized to either the selective A(2A) antagonist KW-6002 or matching placebo capsules in a 6-week dose-rising design (40 and 80 mg/day). Motor function was rated on the Unified PD Rating Scale. RESULTS: KW-6002 alone or in combination with a steady-state IV infusion of each patient's optimal levodopa dose had no effect on parkinsonian severity. At a low dose of levodopa, however, KW-6002 (80 mg) potentiated the antiparkinsonian response by 36% (p < 0.02), but with 45% less dyskinesia compared with that induced by optimal dose levodopa alone (p < 0.05). All cardinal parkinsonian signs improved, especially resting tremor. In addition, KW-6002 prolonged the efficacy half-time of levodopa by an average of 47 minutes (76%; p < 0.05). No medically important drug toxicity occurred. CONCLUSIONS: The results support the hypothesis that A(2A) receptor mechanisms contribute to symptom production in PD and that drugs able to selectively block these receptors may help palliate symptoms in levodopa-treated patients with this disorder. Comment in Nondopaminergic symptomatic therapies for Parkinson's disease: turn on or turn off? [Neurology. 2003] PMID: 12913186 [PubMed - indexed for MEDLINE]