Potassium compounds Amiloride

The salty taste is primarily due to sodium ions acting directly on ion channels. Amiloride specifically blocks sodium channels however, it does not block all responses to salt, in cating more than one mechanism for salty sensation. A different compound, 4-aminopyridine, blocks potassium channels but not sodium. This suggests that receptor proteins and second messengers are not uired, and that these stimuli act directly on ion membrane channels. The physiology of the response of cells to salt has been reviewed (7). 

Many guanidinocarbonyl- and guanidinocarbamoylpyrazines have been prepared and tested for diuretic activity (150, 432, 799, 802, 809, 1058, 1218, 1408). Compounds of these types promote sodium ion excretion but potassium ion excretion is unaffected or repressed. Amiloride (2-amidinocarbamoyl-3,5-diamino-... 

N-Amidinopyrazine carboxamides. The synthesis and biological activity of a great number of compounds of this type were described in a series of papers between 1965 and 1 68 [159—162]. The first of these described the diuretic activity in adrenalectomised DOC A-treated rats of a series of A -amidino-3-amino-6-halopyrazine carboxamides. In the second paper, it was discovered that the introduction of a 5-amino group into the pyrazine ring increased the diuretic potency. One of the compounds, amiloride (A -amidino-3,5-diamino-6-chloro-pyrazine carboxamide (Figure 1.13)) later became widely used in clinical practice, particularly in combination with other diuretics. Its use in combination with diuretics acting more proximally in the nephron is related to the prevention of potassium loss which results when an excess sodium load is delivered to the distal tubule. Thus, amiloride is a potassium-sparing diuretic [163]. 

Amiloride is an orally administered potassium-sparing diuretic that has been used clinically for several decades, most commonly in combination with thiazide (e.g., hydrochlorothiazide) or loop diuretics (e.g., frusemide) as an antikaliuretic. Studies have shown that amiloride is also a moderately potent competitive inhibitor of uPA (Ki = 7 pM) and that uPA inhibition correlates with significant anti-tumor/metastasis effects of the compound in vivo [100]. 

Diuretics represent a heterogeneous class of compounds however, most of them can be measured using conventional absorbance detectors such as UV-analyzers without further derivatization at reasonable detection limits of approximately 0.01-2.0 pg/mL. Increased sensitivity and/or selectivity was reported for the loop diuretics furosemide and bumetanide as well as the potassium sparing diuretics amiloride and triamterene when using fluorescence detection due to the fact that numerous agents co-extracted with diuretics are visualized by means of UV but not fluorescence detection. 

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