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- W1992011275 abstract "It has been well established that the antihypertensive drugs clonidine and methyldopa lower blood pressure by acting on postsynaptic alpha 2-adrenergic receptors within cardiovascular control centers of the brain. A number of novel agents designed as lipophilic and highly selective alpha 2-adrenergic stimulants have been synthesized and in general the pharmacological features of these agents resemble clonidine or alpha-methylnorepinephrine, the principal metabolite of methyldopa. The clonidine analogs, ICI-106,270, UK-14,304, piclonidine (LR-99,853), and the bridge analogs (ST-1913, ST-1966,ST-1967) exhibit varying activity on the central cardiovascular control centers. ICI-106,270 is of interest because relative to clonidine it appears to exert fewer CNS side effects. Azepexole (BHT-933) is also of interest because, although structurally unrelated to clonidine, it appears to interact with central alpha-adrenergic receptors in a manner similar to that of clonidine. In contrast, central administration of ST-1966, a monoatomic bridge analog of clonidine, lowers blood pressure in animals treated with an alpha 2-antagonist, which suggests other mechanisms may be involved in its action. Novel antihypertensive agents structurally similar to methyldopa have not been described, although viable pro-drugs of methyldopa such as 2-oxo-1,3-dioxol-4-yl-methyl and pivaloyloxyethyl esters have been shown to have greater oral activity than methyldopa, presumably because they are more lipophilic than the parent moiety.(ABSTRACT TRUNCATED AT 250 WORDS)" @default.
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- W1992011275 date "1984-09-01" @default.
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- W1992011275 title "New centrally acting antihypertensive drugs related to methyldopa and clonidine." @default.
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- W1992011275 doi "https://doi.org/10.1161/01.hyp.6.5_pt_2.ii51" @default.
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