Rapastinel

Rapastinel is an amidated tetrapeptide, built from four amino acids, that acts as a modulator of the N-methyl-D-aspartate (NMDA) glutamate receptor ^[1]. It was created by Joseph Moskal and colleagues, first at the company Naurex and later Allergan, and was derived from the structure of a monoclonal antibody, B6B21, that influences the same receptor ^[1]. Because it is a peptide, it is not active when taken by mouth and was administered by intravenous injection ^[1].

The compound was investigated chiefly as a treatment for major depressive disorder, particularly cases that had not responded to conventional antidepressants ^[2]. In an early randomized, placebo-controlled proof-of-concept study, a single intravenous dose reduced depressive symptoms within hours, and the benefit persisted for about a week, without the psychotomimetic side effects seen with ketamine ^[2]. On the strength of such findings the drug received Fast Track and Breakthrough Therapy designations from United States regulators. In 2019, however, its Phase III program failed to separate from placebo, and development was discontinued ^[1].

Rapastinel never reached the market and remains an investigational compound of scientific interest for how modulation of the NMDA receptor can produce rapid mood effects ^[1][3]. Its research history is often discussed alongside ketamine as part of the wider effort to develop faster-acting antidepressants ^[3].