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New therapeutic principle for dyskinesia shows clinical effect

Involuntary dyskinetic movements induced by treatment with levodopa (L-dopa) are a common problem for people with Parkinson’s disease. Science Today reports that researchers at Karolinska Institutet and Lund University in Sweden seem to be close to a novel therapy for this distressing side effect. A treatment study published in the scientific periodical Brain shows that a drug that stimulates certain serotonin receptors in the brain counteracts the dyskinesia-causing effects of L-dopa.

The substance tested by the team, eltoprazine, is a so-called serotonin receptor agonist that targets receptor types 5-HT1A and 5-HT1B. Serotonin is a neurotransmitter involved in the regulation of many biological phenomena, such as satiation, sleep and mental wellbeing, as well as movement. Earlier research on animal models for Parkinson’s conducted by Anders Bjorklund, professor of histology at Lund University, and Per Svenningsson, professor of neurology at Karolinska Institutet, showed promising results using serotonin receptor agonists against L-dopa-induced hyperkinesia, and have prompted the researchers to examine if the principle also operates in humans.

The study included 22 patients with protracted and complicated Parkinson’s disease and L-dopa-induced dyskinesia. In the four-way crossover study, patients were given a single tablet of placebo and eltoprazine 2.5, 5 and 7.5 mg, alongside a challenge dose of levodopa that was 1.5 times that of their usual L-dopa dose.

It was found that a 5 mg and 7.5 mg dose of eltoprazine both significantly reduced the patients’ dyskinesia. At the same time, the preparation had no adverse impact on the anti-Parkinsonian effects of the L-dopa treatment. Other than a few patients having some transient episodes of nausea, dizziness and other minor symptoms the treatment was well tolerated

Journal Reference:
P. Svenningsson, C. Rosenblad, K. af Edholm Arvidsson, K. Wictorin, C. Keywood, B. Shankar, D. A. Lowe, A. Bjorklund, H. Widner. Eltoprazine counteracts L-DOPA-induced dyskinesias in Parkinson’s disease: a dose-finding study. Brain, 2015; DOI: 10.1093/brain/awu409

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