SSR-125543 is a potent, selective, and orally active corticotropin-releasing factor 1 receptor (CRF1) antagonist (Ki value of 2nM). SSR-125543 attenuates long-term cognitive deficit induced by acute inescapable stress in mice, independently from the hypothalamic pituitary adrenal axis. SSR-125543 prevents stress-induced cognitive deficit associated with hippocampal dysfunction. SSR-125543 had been in phase II clinical trials by Sanofi for the treatment of Post-traumatic stress disorder. It is also in phase I trials for the treatment of anxiety. The compound had also been in phase II clinical trials for the treatment of major depression. However, in 2011, the research was discontinued.

Pseudohypericin is a predominant naphthodianthrone from St. John’s wort (Hypericum perforatum L.) phytomedicinal drug. It has been shown to specifically inhibit protein kinase C and dopamine-β-hydroxylase. Also, pseudohypericin induces apoptosis and selectively antagonizes corticotropin-releasing factor in murine models. Inhibition of thioredoxin system by pseudohypericin showed appreciable anticancer properties of this natural compound. Pseudohypericin has antiretroviral activity, it has potential therapeutic value in diseases such as AIDS. Pseudohypericin is implicated in the antidepressant efficacy of St. John's wort.

CP 154526 hydrochloride is a selective, non-peptide corticotropin releasing hormone receptor 1 (CRF1) antagonist. CP 154526 readily penetrates the CNS following peripheral administration. In the clinic, CP-154,526 may have important therapeutic utility in treating depression and anxiety as well as other diseases where excessive stimulation of CRF receptors contributes to pathology. The CRF1 receptor antagonist CP-154,526 attenuated the acquisition and prevented the expression of EtOH-induced psychomotor sensitization.