It has been studied as a possible treatment for congestive heart failure, and appears to be well tolerated as such.[3] As of 2012, clinical trials to assess nepicastat as a treatment for post-traumatic stress disorder (PTSD) and cocaine dependence have been completed.[4][5] In Phase 2 study treatment with nepicastat was not effective in relieving PTSD-associated symptoms when compared to placebo. The study was funded by the U.S. Department of Defense.[6] As of October 2024, development has been discontinued for most indications.[1]
Mice lacking epinephrine exhibit reduced contextual memory after fear conditioning .[7] In addition, in PTSDepinephrine enhances traumatic contextual memory.[8] Studies indicate that nepicastat effectively reduces norepinephrine in both peripheral and central tissues in rats[9][10] and dogs.[11] Nepicastat also upregulates the transcription Npas4 and Bdnf genes in the mice hippocampus potentially contributing to neuronal regulation and the attenuation of traumatic contextual memories [12][13] No DBH inhibitor has received marketing approval due to poor DBH selectivity, low potency and side effects, however DBH gene silencing may be an alternative for patients with heightened sympathetic activity.[14] Some studies, however have shown that nepicastat is well-tolerated in healthy adults and no significant differences in adverse events were observed.[15] Given that nepicastat treatment has been proven to be effective in reducing signs in an PTSD mouse model with increased catecholamine levels, [16] it could be a promising treatment option for humans with PTSD characterized by increased catecholamine plasma levels.[17]
^Bonifácio MJ, Sousa F, Neves M, Palma N, Igreja B, Pires NM, et al. (March 2015). "Characterization of the interaction of the novel antihypertensive etamicastat with human dopamine-β-hydroxylase: comparison with nepicastat". European Journal of Pharmacology. 751: 50–58. doi:10.1016/j.ejphar.2015.01.034. PMID25641750.
^Loureiro AI, Bonifácio MJ, Fernandes-Lopes C, Pires N, Igreja B, Wright LC, et al. (2015-09-02). "Role of P-glycoprotein and permeability upon the brain distribution and pharmacodynamics of etamicastat: a comparison with nepicastat". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 45 (9): 828–839. doi:10.3109/00498254.2015.1018985. PMID25915108.
