![]() | |
Names | |
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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
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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 inhibitor of dopamine beta-hydroxylase (DBH), an enzyme that catalyzes the conversion of dopamine to norepinephrine. [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]
![]() | |
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)
|
|
ChEBI | |
ChemSpider | |
MeSH | Nepicastat |
PubChem
CID
|
|
UNII | |
CompTox Dashboard (
EPA)
|
|
| |
| |
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 inhibitor of dopamine beta-hydroxylase (DBH), an enzyme that catalyzes the conversion of dopamine to norepinephrine. [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]