2-(3-Pyridyl)-tetrahydrothiopyran-2-carbothioamide derivatives and analogues: A novel family of potent potassium channel openers

Aloup, Jean-Claude; Farge, D.; James, Clint A.; Mondot, S.; Cavero, Icilio

doi:10.1358/dof.1990.015.11.147141

Cited by 38 publications

(5 citation statements)

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“…Aprikalim, a direct activator of ATP-sensitive potassium channels, 13 dilates the basilar artery (see Refer- ence 12 and the present study). Dilator responses of the basilar artery to norepinephrine and calcitonin generelated peptide are mediated in part by activation of ATP-sensitive potassium channels.…”

Section: Altered Responses To Aprikalimsupporting

confidence: 58%

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ATP-sensitive potassium channels in the basilar artery during chronic hypertension.

1993

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We examined the hypothesis that dilatation of the basilar artery in response to activation of ATP-sensitive potassium channels is impaired in stroke-prone spontaneously hypertensive rats (SHRSP). Changes in basilar artery diameter in response to aprikalim, a direct activator of ATP-sensitive potassium channels, were measured in anesthetized SHRSP and normotensive Wistar-Kyoto (WKY) rats through a cranial window. Topical application of aprikalim increased basilar artery diameter in WKY rats. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, abolished aprikalim-induced vasodilatation.

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Section: Altered Responses To Aprikalimsupporting

confidence: 58%

“…13 Impairment of endothelium-dependent responses during chronic hypertension has been described both in vitro 1 …”

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confidence: 99%

ATP-sensitive potassium channels in the basilar artery during chronic hypertension.

1993

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“…Aprikalim 41 is the prototype [60] of thioformamide KCOs (scheme 7). Thioamide derivatives of several heterocycles, bearing a 2-pyridyl moiety in 2-position, with known antiulcer and antisecretory properties served as precursors.…”

Section: Thioformamidesmentioning

confidence: 99%

Structure-Activity Relationships of KATP Channel Openers

Mannhold¹

2006

CTMC

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Given their many physiological functions, K(ATP) channels represent promising drug targets. Sulfonylureas like glibenclamide block K(ATP) channels; they are used in the therapy of type 2 diabetes. Openers of K(ATP) channels (KCOs) e.g. relax smooth muscle and induce hypotension. KCOs are chemically heterogeneous and include as different classes as the benzopyrans, cyanoguanidines, thioformamides, thiadiazines and pyridyl nitrates. Examples for new chemical entities more recently developed as KCOs include cyclobutenediones, dihydropyridine related structures, and tertiary carbinols. Structure-activity relationships of the main chemical classes of KCOs are discussed.

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“…- 46 Dilation of coronary microvessels in response to aprikalim is inhibited by the ATP-sensitive K + channel inhibitor glibenclamide but not by charybdotoxin or apamin, inhibitors of calcium-activated channels, or inhibitors of nitric oxide synthase.…”

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confidence: 99%

Enhanced coronary vasoconstrictive response to serotonin subsides after removal of dietary cholesterol in atherosclerotic monkeys.

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Piegors

Benzuly

et al. 1994

Arterioscler Thromb

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Constriction in response to serotonin is enhanced in the coronary arteries of atherosclerotic monkeys. The main objective of the present study was to determine whether abnormal responses to serotonin in atherosclerosis are reversed following removal of dietary cholesterol. In addition, we examined the effect of an atherogenic diet and reduction in dietary cholesterol on vascular responses to activation of ATP-sensitive K + channels with aprikalim. Diameters of small coronary arteries were measured on the epicardial surface of the left ventricle in vivo by using stroboscopic illumination synchronized to the heart cycle to visually freeze the motion of the heart. Diameters were measured with a microscope-video system during topical application of two vasoconstrictor agonists, serotonin and the thromboxane mimetic U46619, and the vasodilator agonists aprikalim and nitroprusside. Responses V ascular responsiveness to several agonists is altered by atherosclerosis, 17 and coronary vasoconstrictor responses to serotonin are augmented in patients with atherosclerosis or unstable angina. 56 Coronary microvessels relax in response to serotonin in normal monkeys and constrict in atherosclerotic animals.8 Thus, vasomotor abnormalities of atherosclerosis extend to the coronary microcirculation despite an absence of morphological evidence of disease.8 " A critical question is whether abnormal vascular responses in the atherosclerotic coronary circulation can be restored to normal by reducing dietary cholesterol. Reduction of dietary cholesterol reduces the intimal area of arteries as lipids are reabsorbed from the vessel wall.1214 Fibrosis progresses within the artery, however, so that maximal vasodilator responses do not improve consistently. 13 Nevertheless, studies in the hindlimb and cerebral circulation suggest improvement in vascular function after regression of atherosclerosis, with restoration of endothelium-dependent relaxation 15 and reduction in abnormal vasoconstriction in response to serotonin. 1617 It is unclear whether reductions in dietary cholesterol restore vascular reactivity of the coronary circulation to normal. The major objective of the present study was to determine whether reduction were compared in normal (n=9), atherosclerotic (n=14; highcholesterol diet), and regression (n=8; high-cholesterol diet followed by normal diet) monkeys. Constriction of coronary arteries in response to serotonin was enhanced in monkeys on an atherogenic diet and was normal in regression monkeys. Vasoconstriction in response to U46619 and vasodilation in response to nitroprusside and aprikalim were not altered by atherosclerosis. Thus, abnormal vascular responses to serotonin in small coronary arteries of atherosclerotic monkeys without morphological evidence of disease can be reversed to normal by reducing dietary cholesterol. (Arterioscler Thromb. 1994;14:951-957.) Key Words • serotonin • U46619 • aprikalim • nitroprusside • coronary resistance of dietary cholesterol in atherosclerotic monkeys abolishes v...

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2-(3-Pyridyl)-tetrahydrothiopyran-2-carbothioamide derivatives and analogues: A novel family of potent potassium channel openers

Cited by 38 publications

References 0 publications

ATP-sensitive potassium channels in the basilar artery during chronic hypertension.

ATP-sensitive potassium channels in the basilar artery during chronic hypertension.

Structure-Activity Relationships of KATP Channel Openers

Enhanced coronary vasoconstrictive response to serotonin subsides after removal of dietary cholesterol in atherosclerotic monkeys.

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