Hypertension is the most common
cardiovascular disease. The discovery of the
antihypertensive action of
adenosine triphosphate-sensitive
potassium (K(
ATP)) channel openers was a significant advance in the treatment of
hypertension.
Iptakalim is a novel K(
ATP) channel opener with a unique chemical structure that differs from other K(
ATP) openers. Among the 3 different subtypes of K(
ATP) channels heterologously expressed in human embryonic kidney cells and Xenopus oocytes,
iptakalim exhibits significant selectivity for SUR2B/Kir6.1 channels, mild effects on SUR2A/Kir6.2 channels, and fails to open SUR1/Kir6.2 channels.
Iptakalim is a more potent activator of the SUR2B/Kir6.1 subtype of K(
ATP) channels than
diazoxide and
pinacidil, the 2 most commonly studied K(
ATP) channel openers.
Iptakalim selectively produces arteriolar vasodilation with essentially no effect on the capacitance vessels. It can preferentially relax arterioles and small arteries, without affecting large arteries. Furthermore,
iptakalim strongly lowers the blood pressure of hypertensive rodents and humans but has little effect on normotensive rodents and humans. Selective
antihypertensive action is not observed with
pinacidil or
diazoxide and may be due to the high selectivity of
iptakalim for the SUR2B/Kir6.1 subtype of K(
ATP) channels, as well as its selective relaxation of resistance vessels. In pulmonary arterial smooth muscle cells,
iptakalim inhibits the increase of cytoplasmic free Ca2+ concentration, as well as cell proliferation induced by
endothelin-1. Furthermore,
iptakalim has exerted protective effects against hypertensive damage to target organs in rats and improves endothelial dysfunction associated with
cardiovascular diseases by selective activation of the SUR2B/Kir6.1 subtype of K(
ATP) channels expressed in the endothelium. Clinical trials of
iptakalim in the treatment of mild-moderate
hypertension have been completed in China. In additional to strong
antihypertensive efficacy,
iptakalim seems to have a favorable safety and tolerability profile.
Iptakalim is a promising new generation
antihypertensive drug.