Bench-to-bedside: IRP research leads to brexanolone, first-ever drug specifically for postpartum depression

Approximately 1 in 9 women in the United States experiences symptoms of postpartum depression, according to the Centers for Disease Control and Prevention. Now, the U. S. Food and Drug Administration (FDA) has approved brexanolone, an analog of the endogenous human hormone allopregnanolone and the first drug specifically designed to treat postpartum depression.

Some psychiatric drugs owe their discovery to chance — serendipitous observations of clinical benefit — or a process of incremental improvement based on drugs previously discovered by chance. Not so with brexanolone, which has a truly novel mechanism of action and was developed by design, thanks to a series of basic and translational neuroscience studies. FDA approval represents the final phase of a bench-to-bedside journey for this drug — a journey that began in the NIMH Intramural Research Program (IRP).

In the 1980s, NIMH IRP researchers discovered that metabolites (products formed when the body breaks down or “metabolizes” other substances) of the steroid hormones progesterone and deoxycorticosterone bound to and acted upon receptors for gamma-aminobutyric acid (GABA) — a major inhibitory neurotransmitter in the brain. These steroids were found to amplify GABA-activated chloride ion currents, thereby impacting the excitability of neurons.

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This page was last updated on Friday, January 21, 2022