The novel 5-HT1A receptor agonist, NLX-112 reduces l-DOPA-induced abnormal involuntary movements in rat: A chronic administration study with microdialysis measurements

Neuropharmacology
A C McCrearyAdrian Newman-Tancredi

Abstract

Although l-DOPA alleviates the motor symptoms of Parkinson's disease (PD), it elicits troublesome l-DOPA-induced dyskinesia (LID) in a majority of PD patients after prolonged treatment. This is likely due to conversion of l-DOPA to dopamine as a 'false neurotransmitter' from serotoninergic neurons. The highly selective and efficacious 5-HT1A receptor agonist, NLX-112 (befiradol or F13640) shows potent activity in a rat model of LID (suppression of Abnormal Involuntary Movements, AIMs) but its anti-AIMs effects have not previously been investigated following repeated administration. Acute administration of NLX-112 (0.04 and 0.16 mg/kg i.p.) reversed l-DOPA (6 mg/kg)-induced AIMs in hemiparkinsonian rats with established dyskinesia. The activity of NLX-112 was maintained following repeated daily i.p. administration over 14 days and was accompanied by pronounced decrease of striatal 5-HT extracellular levels, as measured by in vivo microdialysis, indicative of the inhibition of serotonergic activity. A concurrent blunting of l-DOPA-induced surge in dopamine levels on the lesioned side of the brain was observed upon NLX-112 administration and these neurochemical responses were also seen after 14 days of treatment. NLX-112 also supp...Continue Reading

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Jul 9, 2016·Progress in Neurobiology·Philippe De DeurwaerdèreMark J Millan
May 2, 2017·ACS Chemical Neuroscience·Philippe HuotAndrew C McCreary
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Dec 24, 2021·Neurodegenerative Disease Management·Philippe HuotCynthia Kwan

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