Distinct roles of NMDA receptor GluN2 subunits in the effects of ketamine and its enantiomers

Abstract

The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine is known to induce various pharmacological effects. It has attracted attention because of its rapid and sustained antidepressant effects in depressed patients, although its side effects have raised some concerns. NMDA receptors are considered to mediate various effects of ketamine, but other systems may be involved. NMDA receptors are di-heteromeric complexes that are composed of two GluN1 subunits and two homomeric GluN2A-D/3A subunits, or tri-heteromeric complexes that are composed of two GluN1 subunits and two heteromeric GluN2A-D/GluN3A, B subunits. The involvement of each NMDA receptor subunit in the neural mechanisms that underlie the various effects of ketamine remains unclear. This chapter focuses on GluN2 subunits and discusses the involvement of each GluN2 subunit in various pharmacological actions of ketamine.