Nepicastat hydrochloride

• CAS: 170151-24-3
• Catalog Number: ACM170151243
• Category: Main Products
• Molecular Weight: 331.81
• Molecular Formula: C14H16ClF2N3S
• Synonyms: Nepicastat HCl
• Appearance: White to Beige ; Powder

Case Study

Effects of Nepicastat on Enzyme Activity and Dopamine and NorepinephrineLevels in Rats

Catelas, Diogo Nóbrega, et al. Clinical and Experimental Hypertension, 2020, 42(2), 118-125.

Nepicastat functions as a selective dopamine β-hydroxylase (DβH) inhibitor which reduces norepinephrine (NE) levels and boosts dopamine (DA) levels in cardiovascular tissues. Researchers examined nepicastat's impact on DβH enzymatic activity and DA and NE levels within rat adrenal glands as well as left ventricles and kidneys.
· Methods: The DβH assay involved converting tyramine into octopamine through enzymatic hydroxylation and measuring DA and NE tissue levels by HPLC-ED.
· Results: Nepicastat (30 mg/kg, p.o.) The adrenals exhibited a decrease of 93% and 80% in DβH activity at 4 hours and 8 hours after drug treatment, which resulted in significant drops in NE and epinephrine tissue levels while causing DA levels to rise along with the DA/NE tissue ratio and similar measurements for NE, DA and DA/NE tissue ratios were observed in the left ventricle and kidney. The left ventricle and kidney DβH activity levels exhibit too much variability to validate the impact of nepicastat on catecholamine tissue levels.
· Conclusion: DβH activity measurement in heart and kidney tissues fails to meet robustness standards but adrenal DβH activity serves as a reliable marker. The effect size induced by nepicastat on DA/NE tissue ratios measured as an indirect DβH activity marker displayed similar results across sympathetically innervated tissues like the left ventricle and kidney as well as the adrenal medulla.

Evaluation of Nepicastat Treatment to Improve Symptoms of Post-Traumatic Stress Disorder in Animal Models

Martinho, Raquel, et al. Frontiers in Molecular Neuroscience, 2021, 14, 745219.

Post-traumatic stress disorder (PTSD) affects patients by raising their plasma and urine levels of both norepinephrine and epinephrine. Dopamine-β-hydroxylase (DBH) transforms dopamine into norepinephrine which means blocking DBH results in reduced catecholamine levels. This research focused on assessing the effectiveness of nepicastat treatment in reducing PTSD symptoms within an animal model.
· Evaluation Methods
Female wild-type (129x1/SvJ) mice underwent a PTSD induction protocol. They received either the DBH-inhibitor nepicastat (30 mg/kg) or a vehicle (0.2% HPMC) daily from day 0 to either day 7 or 12. Freezing behavior was measured on days 0, 1, 2, and 7, and various behavioral tests were conducted. Nepicastat levels in plasma and DBH activity in the adrenal gland were assessed. Catecholamine levels were measured using HPLC with electrochemical detection, and the mRNA expressions of Npas4 and Bdnf in the hippocampus were analyzed via qPCR. Mice in the PTSD group treated with nepicastat exhibited reduced freezing behavior and an increased duration and frequency of entries into the open arms of the elevated plus maze test.
· Evaluation Results
The treatment with nepicastat led to decreased adrenal gland DBH activity and reduced plasma catecholamine levels in mice. Elevated mRNA expression levels of Npas4 and Bdnf in the hippocampus appeared in these mice by the seventh day. The DBH inhibitor nepicastat demonstrated effectiveness in reducing both traumatic memories and anxiety-related behaviors in this mouse model for PTSD. Alleviating PTSD symptoms may depend on disrupting how traumatic memories form, consolidate, retrieve, and express themselves.