Pridopidine Reverses Phencyclidine-Induced Memory Impairment

• Published in: Frontiers in pharmacology Vol. 9; p. 338
• Main Authors: Sahlholm, Kristoffer, Valle-León, Marta, Fernández-Dueñas, Víctor, Ciruela, Francisco
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media 10.04.2018; Frontiers Media S.A
• Subjects: Assaigs clínics; Central nervous system diseases; Clinical trials; cognition; Dopamina; Dopamine; dopamine stabilizers; Malalties del sistema nerviós central; Malalties neurodegeneratives; Medicin och hälsovetenskap; mice; Neurodegenerative Diseases; Pharmacology; phencyclidine; sigma-1 receptor; phencyclidine; sigma-1 receptor; dopamine stabilizers; cognition; mice
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2018.00338

Pridopidine is in clinical trials for Huntington's disease treatment. Originally developed as a dopamine D receptor (D R) ligand, pridopidine displays about 100-fold higher affinity for the sigma-1 receptor (sigma-1R). Interestingly, pridopidine slows disease progression and improves motor function in Huntington's disease model mice and, in preliminarily reports, Huntington's disease patients. The present study examined the anti-amnesic potential of pridopidine. Thus, memory impairment was produced in mice by administration of phencyclidine (PCP, 10 mg/kg/day) for 10 days, followed by 14 days' treatment with pridopidine (6 mg/kg/day), or saline. Finally, novel object recognition performance was assessed in the animals. Mice receiving PCP and saline exhibited deficits in novel object recognition, as expected, while pridopidine treatment counteracted PCP-induced memory impairment. The effect of pridopidine was attenuated by co-administration of the sigma receptor antagonist, NE-100 (10 mg/kg). Our results suggest that pridopidine exerts anti-amnesic and potentially neuroprotective actions. These data provide new insights into the therapeutic potential of pridopidine as a pro-cognitive drug.