TY - JOUR T1 - Effects of a novel psychomotor stabilizer, IRL790, on biochemical measures of synaptic markers and neurotransmission JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.119.264754 SP - jpet.119.264754 AU - Kristina Becanovic AU - Maria Vittoria de Donno AU - Vasco Sousa AU - Joakim Tedroff AU - Per Svenningsson Y1 - 2020/01/01 UR - http://jpet.aspetjournals.org/content/early/2020/05/01/jpet.119.264754.abstract N2 - The novel small-molecule, IRL790, a psychomotor stabilizer is currently in clinical trial for treatment of levodopa induced dyskinesia and psychosis in patients with Parkinson's disease. Here, we used naive mice to investigate the effects of acute systemic administration of IRL790 on protein levels and phosphorylation states of proteins relevant for synaptic plasticity and transmission. IRL790 increased proBDNF protein levels and phosphorylation at Ser1303 of the NR2B in prefrontal cortex. IRL790 also increased the phosphorylation states at Ser19, Ser31, Ser40, respectively, of tyrosine hydroxylase (TH) in striatum. IRL790 reduced protein levels of the NR2B-receptor in striatum, but not in prefrontal cortex. Taken together, we report that systemically administered IRL790 rapidly elicits changes in protein level and phosphorylation state of proteins associated with a beneficial effect on synaptic markers and neurotransmission.SIGNIFICANCE STATEMENT The novel small-molecule, IRL790, a psychomotor stabilizer is currently in clinical trial for treatment of levodopa induced dyskinesia and psychosis in patients with Parkinson’s disease. In this study, we report that systemically administered IRL790 rapidly elicits changes in protein level and phosphorylation state of proteins associated with a beneficial effect on synaptic markers and neurotransmission. ER -