Combined 5-HT2A and mGlu2 modulation for the treatment of dyskinesia and psychosis in Parkinson's disease.

Combined 5-HT2A and mGlu2 modulation for the treatment of dyskinesia and psychosis in Parkinson's disease. Neuropharmacology. 2021 Jan 21;:108465 Authors: Kwan C, Frouni I, Nuara SG, Belliveau S, Kang W, Hamadjida A, Bédard D, Beaudry F, Panisset M, Gourdon JC, Huot P Abstract Antagonising the serotonin 2A (5-HT2A) receptor is an efficacious way to alleviate dyskinesia and psychosis in Parkinson's disease (PD). However, previous research indicates that there might be a limit to the effects conferred by this approach. 5-HT2A receptors were shown to form hetero-dimers with metabotropic glutamate 2 (mGlu2) receptors, in which 5-HT2A blockade and mGlu2 activation elicit equivalent effects at the downstream signalling level. We have previously shown that mGlu2 activation reduces both dyskinesia and psychosis-like behaviours (PLBs) induced by L-3,4-dihydroxyphenylalanine (L-DOPA), in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. Here, we hypothesised that concurrent 5-HT2A antagonism and mGlu2 activation would provide greater anti-dyskinetic and anti-psychotic benefits than either approach alone. We conducted 3 series of experiments in the MPTP-lesioned marmoset. In the first series of experiments, the mGlu2 positive allosteric modulator LY-487,379 and the 5-HT2A antagonist EMD-281,014, either alone or in combination, were added to L-DOPA. In the second series of experiments, the mGlu2/3 orthosteric agonist LY-...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research