Pridopidine

Potential treatment for Huntington’s disease, Parkinson’s disease, and schizophrenia (1,2). Able to reverse both hypo- and hyperdopaminergia depending on local dopamine concentrations without inducing catalepsy. This was originally attributed to functional dopamine D2 antagonism with fast on/off kinetics (“dopamine stabilizer”) (3). More recent studies have attributed pridopidine’s effects to its being a more potent sigma-1 ligand than a D2 ligand (4,5). Displays neuroprotective/restorative effects (6,7) and ameliorates central features of amyotrophic lateral sclerosis pathology (8) in a sigma-1-mediated manner.

1. F Pettersson et al. 2010 J. Med. Chem. 53:2510. 2. S Natesan et al. 2006 J. Pharmacol. Exp. Ther. 318:810. 3. T Dyhring et al. 2010 Eur. J. Pharmacol. 628:19. 4. K Sahlholm et al. 2015 Psychopharmacology (Berl) 232:3443. 5. K Sahlholm et al. 2013 Mol. Psychiatry 18:12. 6. V Francardo et al. 2019 Neurotherapeutics 16:465. 7. D Ryskamp et al. 2017 Neurobiol. Dis. 7 97(Pt A):46. 8. A Ionescu et al. 2019 Cell Death Dis. 10:210.