In the last four decades, the several classes of diuretics, currently available for
clinical use, have been the first line option for the therapy of widespread cardiovascular
and non-cardiovascular diseases. Diuretic drugs generally exhibit an overall favourable
risk/benefit balance. However, they are not devoid of side effects. In particular, all the
classes of diuretics cause alteration of potassium homeostasis.
In recent years, understanding of the physiological role of the renal outer medullary potassium
(ROMK) channels, has shown an intriguing pharmacological target for developing
an innovative class of diuretic agents: the ROMK inhibitors. This novel class is expected
to promote diuretic activity comparable to (or even higher than) that provided by the
most effective drugs used in clinics (such as furosemide), with limited effects on potassium
In this review, the physio-pharmacological roles of ROMK channels in the renal function are
reported, along with the most representative molecules which have been currently developed
as ROMK inhibitors.