Minoxidil sulphate

Minoxidil sulphate is a potent activator of the ATP-modulated potassium channel and thereby relaxes vascular smooth muscle to give a resultant antihypertensive effect. The actual sulphate metabolite is a relatively minor metabolite, the principal... 

Despite these challenges, the area of K+ channel openers (PCOs) is emerging as an active area of drug design. Over the past 5-10 years, eight novel structural classes of PCOs have received systematic development benzopyrans (e.g., cromakalim, 7.27), cyanoguanidines (e.g., pinacidil, 7.28), thioformamides (e.g., aprikalim, 7.29), pyridyl nitrates (e.g., nicorandil, 7.30), benzothiadiazines (e.g., diazoxide, 7.31), pyrimidine sulphates (e.g., minoxidil sulphate, 7.32), tertiary carbinols, and dihydropyridines. These various classes have been subjected to analog preparation with compound optimization via structure-activity studies. 

This topic has been reviewed both generally [9], and specifically for variation in the benzopyran nucleus [10]. SARs have also formed part of several comprehensive and useful reports and reviews [11-15], while full details of lead and development KCAs are regularly updated in a useful compilation [16] devoted to modulators of K channels. Hence, this section will address recent advances, and those previously reported [9, 10], where further detail is now available. These are best presented in terms of the different series of KCAs based on the prototype molecules, cromakalim (1), RP 49356 (4), pinacidil (6), and nicorandil (7) that, together with the older compounds, minoxidil sulphate (8) and diazoxide (9), now recognized as KCAs, illustrate the widening range of structural types of this classification... 

The binding studies [66] also highlighted that minoxidil sulphate (8), in contrast to the other KCAs, showed no correlation between its ability to displace [ H]-P1060 (47) binding and its functional effects, supporting the suggestion that this compound opens a different K channel. 

Unlike morphine, minoxidil [26] is not active itself but is metabolized by hepatic sulphotransferases to minoxidil N-0 sulphate (Figure 7.27). 

Minoxidil is a vasodilator selective for arterioles rather than for veins, similar to diazoxide and hydralazine. Like the former, it acts through its sulphate metabolite as an ATP-dependent potassium channel opener. It is highly effective in severe hypertension, but causes increased cardiac output, tachycardia, fluid retention and hypertrichosis. The hair growth is generalised and although a cosmetic problem in women, it has been exploited as a topical solution for the treatment of baldness in men. 

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