Potassium channel openers
Another practically important class of drugs that also in-teract with the sulfonylurea receptor are potassium channel openers. In keeping with our expectations, they will reduce membrane excitability. These are mostly targeted at the Kir channels in the vascular smooth muscle cells (Figure 5.13).
A reduction of smooth muscle tension in the vessel walls will reduce the blood pressure, and high blood pressure ac-cordingly is the usual rationale for their use. Their binding sites on the receptor molecule may be the same as those of the sulfonylurea derivatives, or not; correspondingly, they may or may not resemble the latter drugs in structure (Fig-ure 5.14). The similarity is apparent with diazoxide. This drug actually also affects the pancreatic β-cells, and accord-ingly brings about reduced insulin secretion and elevated blood glucose, rendering it unsuitable for long-term use. The second drug shown (minoxidil) does not have this side effect. It interesting for two reasons:
1. It is a `pro-drug' – it is not minoxidil itself that mediates the pharmacological effect but minoxidil sulfate, which is formed in the liver by a sulfotransferase (the sulfate will replace the oxygen, Figure 5.14) – an example of an active drug metabolite. Relying on drug activation usually adds some variability to the clinical effect of a drug (there may be competing metabolic pathways …), so one would normally prefer a drug that is immediately active. Can you see a reason why one would still prefer minoxidil over the sulfate?
2. One of the side effects of minoxidil is `hypertrichosis', meaning increased hair growth, and consequently many patients refuse it. Strangely, however, the very same side effect has proven highly popular with some patients.
Local application of the drug to balding areas is reportedly effective, too, although the beneficial effect ceases with discontinuation.
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