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| Names | |
|---|---|
| Preferred IUPAC name
5-(Aminomethyl)-1-[(2S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-1,3-dihydro-2H-imidazole-2-thione | |
| Other names
SYN-117 | |
| Identifiers | |
3D model (JSmol) |
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| ChEBI | |
| ChemSpider |
|
| MeSH | Nepicastat |
PubChem CID |
|
| UNII | |
CompTox Dashboard (EPA) |
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| |
| Properties | |
| C14H15F2N3S | |
| Molar mass | 295.35 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
Nepicastat (INN, codenamed SYN117, RS-25560-197) is an inhibitorofdopamine beta-hydroxylase (DBH), an enzyme that catalyzes the conversion of dopaminetonorepinephrine.[1]
It has been studied as a possible treatment for congestive heart failure, and appears to be well tolerated as such.[2] As of 2012, clinical trials to assess nepicastat as a treatment for post-traumatic stress disorder (PTSD) and cocaine dependence have been completed.[3][4] 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.[5]
Mice lacking epinephrine exhibit reduced contextual memory after fear conditioning .[6] In addition, in PTSD epinephrine enhances traumatic contextual memory.[7] Studies indicate that nepicastat effectively reduces norepinephrine in both peripheral and central tissues in rats[8] [9] and dogs.[10] 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 [11][12] 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.[13] Some studies, however have shown that nepicastat is well-tolerated in healthy adults and no significant differences in adverse events were observed.[14] Given that nepicastat treatment has been proven to be effective in reducing signs in an PTSD mouse model with increased catecholamine levels, [15] it could be a promising treatment option for humans with PTSD characterized by increased catecholamine plasma levels.[16]
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