Mesdopetam
Mesdopetam is a dopamine D2 and [D3 receptor|D3 receptor] antagonist with preference for the D3 receptor which is under development for the treatment of Parkinson's disease, drug-induced dyskinesia, and psychotic disorders. It has been described by its developers as having "psychomotor stabilizing" properties.
Pharmacology
The described intention behind mesdopetam was to develop a novel dopamine D2 and D3 receptor antagonist based on agonist- rather than antagonist-like structural motifs and with agonist-like physicochemical properties. It was hypothesized that this would result in an antagonist with specific dopamine receptor interactions more similar to those of agonists like dopamine but without any intrinsic activity, in turn resulting in different in vivo effects than conventional dopamine receptor antagonists. Specifically, antidyskinetic and antipsychotic effects with fewer or no motor side effects was sought. There is also extensive preclinical research to suggest that D3 receptor antagonists reduce levodopa-induced dyskinesia without compromising the antiparkinsonian effects of levodopa.Mesdopetam has 6- to 8-fold preference for the dopamine D3 receptor over the dopamine D2 receptor. It displays a paradoxical agonist-like binding mode in spite of its lack of activational efficacy. By antagonizing D3 autoreceptors, D3 receptor antagonists like mesdopetam have been found to disinhibit dopamine release in the prefrontal cortex, ventral tegmental area, and striatum, which might be involved in the possible therapeutic benefits of these agents. The drug is also a ligand of the sigma σ1 receptor and has some affinity for certain serotonin receptors including the serotonin 5-HT1A and 5-HT2A receptors. In animals, mesdopetam has no effect on spontaneous locomotor activity at assessed doses but antagonizes levodopa-induced dyskinesia and reduces dextroamphetamine- and dizocilpine-induced locomotor hyperactivity.