Losartan carboxylic acid

Description

Losartan carboxylic acid is a physiologically active metabolite of losartan , produced by cytochrome P450 isoforms in the liver. Like the parent compound, losartan carboxylic acid is a potent AT₁ antagonist (K_is = 0.57 and 0.67 nM for rat and human forms, respectively), producing a depressor response and vasodilatation. When administered intravenously, losartan carboxylic acid is more potent and has a longer duration of action than losartan. However, the metabolite has very low oral bioavailability. Losartan, but not its metabolite, inhibits platelet aggregation in vitro.

Chemical Properties

Light-Yellow Solid

Uses

Losartan carboxylic acid is used as a metabolite of Losartan.

Definition

ChEBI: A biphenylyltetrazole that is losartan with the hydroxymethyl group at position 5 on the imidazole ring replaced with a carboxylic acid.

in vitro

e-3174 potently blocked the specific binding of [125i]-aii to vsmc isolated from rat aorta. e-3174 was able to dampen the platelet-derived growth factor-induced increase in cell dna synthesis and protein, which led to the blockade of the aii-induced increase in cell protein [1].

in vivo

rats were administrated e-3174 intravenously at a dose of l.0 mg/kg. after 6 hours, e-3174 markedly attenuated the cardiovascular effects of aii in rats. e-3174 induced a progressive fall in mean arterial pressure and a marked increase in renal flow only [2].

storage

Store at -20°C

References

[1]. li, x. & widdop, r. angiotensin type i receptor antagonists cy-11974 and exp 3174 cause selective renal vasodilatation in conscious spontaneously hypertensive rats. clinical science, 1996; 91(2): 147-154.
[2]. sachinidis, a., ko, y., weisser, p., zu bricbkwedde, m., dsing, r., & christian, r. et al. exp3174, a metabolite of losartan (mk954, dup753) is more potent than losartan in blocking the angiotensin ll-induced responses in vascular smooth muscle cells. journal of hypertension. 1993; 11(2): 155-162.