Crinecerfont (SSR-125543) is a highly potent, selective, and orally bioavailable antagonist of corticotropin-releasing factor 1 receptor (CRF1) with pKis of 8.73 and 9.08 for human cloned or native CRF1 receptors, respectively. SSR125543 attenuates long-term cognitive deficit induced by acute inescapable stress in mice, independently from the hypothalamic pituitary adrenal axis. SSR125543 prevents stress-induced cognitive deficit associated with hippocampal dysfunction.