The recent development and the present status of K+ channel opener

Abstract

The development of vasodilator drugs that open the K+ channels in blood vessels has been of great academic and practical interest. The discoveries of the ATP-sensitive K+ channel and the glibenclamide-sensitive K+ channel have promoted these interests. In relation to this channel, the cardioprotective effectiveness of a K+ channel opener (Aprikalim) in doses that did not change haemodynamics or collateral blood flow were demonstrated in infarct dog heart. The effects were antagonized by glibenclamide. Thus, ATP-sensitive K+ channels seem to play an important role in this effect. Clinical evaluations of the K+ channel openers are reviewed. The hypotensive effects of the drugs are well-recognized. At present, however, the clinical usefulness of K+ channel openers has not been accepted widely, because of their side-effects including reflex tachycardia, edema, flushing and headache. An approach to reduce these side-effects is critical if these K+ channel openers are to be used as good hypotensive drugs. The K+ channel opener nicorandil has been evaluated as a highly effective antianginal drug. It seems likely that the clinical benefits of nicorandil result from both its K+ channel opening properties and its ability to stimulate smooth muscle guanylate cyclase. Clinical data on the pure-selective K+ channel opener cromakalim (lemakalim) as an antianginal drug is limited. However, on the basis of the vasodilator profile of this drug, it is expected to be useful for this purpose. The application of K+ channel openers to treat other disorders such as bladder instability is limited because of its hypotensive action.