Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 (ET-1) production in vitro by interfering with the transcription of the pre-pro-ET-1 gene.
Aminaftone inhibits Endothelin-1 (ET-1) production in cell cultures by interfering with transcription of the pre-pro-endothelin-1 (PPET-1) gene. Incubation with IL-1beta increases concentrations of ET-1 and PPET-1 relative gene expression. Incubation with Aminaftone significantly reduces production of ET-1 in a concentration-dependent manner. A strong direct correlation is found between ET-1 concentrations and PPET-1 relative gene expression, but Aminaftone does not influence endothelin-converting enzyme (ECE) activity[1].
The rats are randomly assigned to the following experimental groups: Control; Monocrotaline; Aminaftone 30 mg/kg/day; Aminaftone 150 mg/kg/day. After 5 weeks, mortality is significantly lower in the animals treated with Aminaftone at both doses compared to Monocrotaline alone. Aminaftone reduces plasma concentration of ET-1 and seems to reduce right heart hypertrophy and the wall thickness of the pulmonary arteries at the highest dose. At the end of the experiment, no rats die in the control and Aminaftone 150 groups, while mortality is 38% in the Monocrotaline group and 13% in the Aminaftone 30 group. Overall, Aminaftone treated rats have a significantly lower mortality compared to rats in the Monocrotaline group (P=0.044)[2].
[1]. Scorza R, et al. Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 production in ECV304 Cells: an in vitro Study. Drugs R D. 2008;9(4):251-7. [2]. Zambelli V, et al. Efficacy of aminaftone in a rat model of monocrotaline-induced pulmonary hypertension. Eur J Pharmacol. 2011 Sep 30;667(1-3):287-91.