Rapastinel, a novel glutamatergic agent with ketamine-like antidepressant actions: Convergent mechanisms.
Pharmacology, Biochemistry and Behavior November 13, 2019 Taro Kato, R. Duman
Ketamine produces rapid (within hours) and long-lasting (7 to 10 days) antidepressant effects by blocking NMDA receptor channels. Rapastinel, a novel glutamatergic compound that acts as an NMDAR partial agonist, also produces rapid antidepressant actions in depressed patients and preclinical rodent models without ketamine-like side effects such as cognitive impairment and psychotomimetic symptoms. Despite recent negative clinical trials, rapastinel may still prove effective as an alternative rapid-acting antidepressant with reduced side effects. This review discusses rapastinel's pharmacological profile and the molecular and cellular mechanisms underlying its rapid and sustained antidepressant actions.