Dopamine beta-hydroxylase is an enzyme that catalyzes the conversion of dopamine to norepinephrine. Nepicastat hydrochloride is a dopamine β-hydroxylase inhibitor with IC50 of 8.5 ± 0.8 and 9.0 ± 0.8 nM for bovine and human, respectively[3]. In vitro, Nepicastat hydrochloride exhibited selective and concentration-dependent inhibition to dopamine-β-hydroxylase in cattle and humans, with IC50 value of 8.5 nM and 9.0 nM, respectively. Nepicastat hydrochloride has quite low affinity for 12 other enzymes and 13 neurotransmitter receptors. In vivo, in the arteries, the left ventricle, and the cerebral cortex of rats with spontaneous hypertension (SHRs), Nepicastat dosage dependently decreased the level of norepinephrine, and increased the dopamine content and dopamine/norepinephrine ratio[3]. In rat brains, 50 mg/kg (i.p.) dose of Nepicastat hydrochloride led to reduction in the noradrenalin (NE), and block of the recovery of cocaine induced drug addiction [4]. In dogs with chronic heart failure, low doses of nepicastat (0.5 mg/kg) are quite suitable to prevent dysfunction and remodeling of the left ventricle (LV), and the combination of nepicastat hydrochloride and enalapril is quite suitable to use in addition to all morphological characteristics[5]. Nepicastat hydrochloride (3 mg/kg, i.v.), to be quite suitable for the use in SHRs anesthesia, plays the role of antihypertensive; it significantly reduces renal vascular resistance (38%) and increases renal blood flow (22%)[6].
搜索
