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• W1982645492 abstract "The number and the pharmacological activities of drugs featuring a guanidine group is actually amazing. Many synthetic guanidine derivatives have attracted pharmacologists in search of new antihypertensive drugs for their ability to block adrenergic nerve activity through central and / or peripheral mechanisms. As a result, compounds such as guanethidine, guanabenz, guanfacine, and pinacidil have been introduced in antihypertensive drug therapy. A crude methanol extract of the Venezuelan plant Verbesina caracasana Fries (Compositae), intravenously administered to mice, was found to induce biological effects such as erection of hair, initial stimulation and subsequent blockade of breathing. Biologically controlled purification yielded a series of active guanidine derivatives, namely G1-G7, which were extensively studied with the focus on the following items: The structure determination of the active compounds by spectral data and a set of reactions; -The confirmation of the structures by a biogenetically oriented synthesis; -The study of the pharmacological profiles of the isolated drugs; -The synthesis of analogous and homologous products in the effort to shed some light on the structureactivity relationship. The metabolites of V.caracasana were characterized, in anesthetized rats, as hypotensive drugs of high (G2), mild (G1, G7) and low (G3,G5,G6) potency, devoid of consistent actions in heart rate, and provided with moderate stimulatory effects on cardiac inotropism and breathing (at selected non-toxic intravenous doses). Autonomic neurogenic components and / or peripheral adrenergic and cholinergic receptor-related pathways were involved in the cardiovascular effects. Synthetic analogs and homologs of G1 and G5 were all shown to be hypotensive drugs of low-mild potency, not affecting appreciably cardiac inotropism and / or breathing. The pharmacodynamic differences among the studied compounds were likely to depend on their ability to cross the blood-brain barrier, lipophilicity and pharmacokinetics. Since most of the compounds did not induce reflex tachycardia and depression of myocardial contractility as the majority of the antihypertensive drugs, they might be useful in the treatment of arterial hypertension of various genesis. Keywords: verbesina caracasana, guanidine derivatives, synthesis, cardiovascular and respiratory systems, pharmacological profiles, antihypertensive therapy." @default.
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• W1982645492 date "2003-09-01" @default.
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• W1982645492 title "Novel Hypotensive Agents from Verbesina Caracasana: Structure, Synthesis and Pharmacology" @default.
• W1982645492 doi "https://doi.org/10.2174/0929867033456990" @default.
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