ischaemic preconditioning of the human heart. - Leicester Research ...

K %-j-p activation is already enhanced, eg. reduced intracellular ATP caused by
ischaemia/hypoxia, and thereby appear to have useful property of targeting ischernic
tissues. The consequences of the interaction of K,.
%-I, p channel openers, the ATP
concentration and other metabolic regulators, is that K. \.,.,, channel openers are much
more potent dufing periods of ischerma or hypoxia. It is not yet known whether the drug
receptor that K., -I-p channel openers act upon is the K%.
I-p channel itself or a separate
protein.
The first generation of these compounds lacked selectivity [13], but the newer
compounds being developed are more likely to be tissue selective, and therefore have
greater therapeutic potential. The profound vasodilatory effect induced by the early K, %ri,
channel openers may be due to their almost exclusive action on vascular smooth muscle,
thereby limiting their use in patients. Newer agents have been proposed, eg BMS 180884,
which appear to be cardioselective but have been shown to cause profound side effects
and thus their clinical application has not succeeded.
At present in the UK, the only licensed KATP channel opener for patient use is
nicorandil. Nicorandil is commercially available for the treatment of angina pectons, but
has not been shown to be superior to placebo when used as monotherapy [292]. At
present, there is an on-going multi-center clinical tnal investigating nicorandil as a
treatment for angina pectons as a second line drug (IONA Study) and this is expected to
yield its interim analysis in the next year. The K..
%-I-p channel opener activity of nicorandil
causes an indirect blockade of calcium channels, and dilatation of arterial resistance
vessels. In addition, the nitrate group activates guanylate cyclase, which causes an
increase in intracellular cyclic guanosine monophosphate (cGMP) leading to dilatation of
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