Is there a therapeutic future for "potassium channel openers'?
1. Potassium channels, which control cell electrical activity, are among the most regulated of all ion channels in biology. Promotion of activity in K+ channels by a wide range of physiological factors tends to stabilize cell function. 2. The discovery of synthetic molecules (e.g. cromakalim) that 'directly' open ATP-sensitive K+ channels has led to a new direction in pharmacology. ATP-sensitive K+ channel-opening properties have subsequently been demonstrated in a diverse range of chemical structures (synthetic and endogenous). 3. The existence of so many different subtypes of K+ channels has been an impetus in the search of new potassium channel openers with different channel selectivities and thus biological profiles. 4. The decrease in cell excitability following K+ channel opening implies a broad clinical potential in a number of pathological conditions for K+ channel openers. Preclinical and clinical evidence supports therapeutic roles of K+ channel openers in disorders of a wide range of biological cells. 5. Although lack of selectivity of current compounds remains a major hurdle, advances in K+ channel openers and K+ channel pharmacology are encouraging. Differences already observed in the pharmacology of K+ channel openers are important factors for the development of second-generation compounds, when tissue selectivity is sought. 6. The availability of subtype-selective K+ channel openers will facilitate detailed study, through a combined effort of electrophysiology, functional pharmacology and molecular biology, leading to focused therapeutic approaches for defined pathological conditions.
Lawson
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D000255:Adenosine Triphosphate / Q000502:physiology; D001578:Benzopyrans / Q000627:therapeutic use*; D001927:Brain Diseases / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D019806:Cromakalim; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D008171:Lung Diseases / Q000188:drug therapy; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000627:therapeutic use*; D001745:Urinary Bladder Diseases / Q000188:drug therapy
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000255:Adenosine Triphosphate