Biochemical inhibition of dopamine-β-hydroxylase
Biochemical assay · Bovine adrenal enzyme and human enzyme purified from SK-N-SH culture medium; cell-free activity assay. [1]
Nepicastat inhibited both enzyme preparations. The R-enantiomer was less potent. The tested off-target panel showed much weaker activity; this does not establish universal selectivity.
| Endpoint | Reported result | Reference |
|---|---|---|
| Bovine dopamine-β-hydroxylase inhibition | IC50 8.5 ± 0.8 nM (mean ± s.e.mean) | [1] |
| Human dopamine-β-hydroxylase inhibition | IC50 9.0 ± 0.8 nM (mean ± s.e.mean) | [1] |
| R-enantiomer comparison | IC50 RS-25560-198: bovine 25.1 ± 0.6 nM; human 18.3 ± 0.6 nM (mean ± s.e.mean) | [1] |
| Activity at the tested off-target enzyme and receptor panel | IC50 or Ki >10 µM | [1] |
Literature-Reported Treatment Conditions
- Exposure duration
- 30–40 min incubation
- Method
- Cell-free enzyme assay with no-inhibitor controls and R-enantiomer comparison.
- Reported limits
- Concentration series and replicate count not specified in the retrieved assay text. Methods contain both 32°C and 37°C statements; a single assay temperature is not asserted.
Methods and source locations
Compound reported in the paper: Nepicastat hydrochloride; Compound label in the paper: RS-25560-197; S-enantiomer
Original-material biochemical evidence; no Adooq lot validation.
Methods—In vitro studies, Drugs, Statistical analysis; Results—In vitro studies
Bovine dopamine-β-hydroxylase inhibition: Tyramine-to-octopamine conversion measured by HPLC; activity relative to no-inhibitor controls; four-parameter fit. — Methods—In vitro studies, Drugs, Statistical analysis; Results—In vitro studies
Human dopamine-β-hydroxylase inhibition: Same cell-free activity assay using human enzyme. — Methods—In vitro studies, Drugs, Statistical analysis; Results—In vitro studies
R-enantiomer comparison: Matched assay comparator; these values describe the R-enantiomer. — Methods—In vitro studies, Drugs, Statistical analysis; Results—In vitro studies
Activity at the tested off-target enzyme and receptor panel: Assay-dependent inhibition or binding endpoints; not a DBH treatment dose. — Methods—In vitro studies and Table 1; Results—In vitro studies