Guanabenz and methyldopa on hypertension and cardiac performance

Abstract

In previous placebo-controlled studies, guanabenz was shown to be a safe and effective antihypertensive drug without acute effects on cardiac function. In view of its therapeutic advantages, a double-blind comparison of guanabenz with methyldopa was performed in a group of 36 patients over 6 mo. Both drugs produced statistically and clinically significant decreases in blood pressure with similar side effects. No laboratory or electrocardiographic abnormalities were found other than positive Coombs' tests which developed in 3 patients during methyldopa therapy. Cardiac performance in 26 of the patients, as measured by noninvasive techniques, showed no significant changes from either drug except for a progressive and statistically significant increase in systolic time interval (QS2) and the ratio of the pre-ejection period to left ventricular ejection time (PEP/LVET) during methyldopa therapy. For an additional 6 mo, continued efficacy and safety were shown under open conditions in those patients who had received guanabenz. The study suggests that guanabenz may be an important new antihypertensive drug because of effectiveness, absence of adverse cardiac effects, and paucity of side effects.

Indoramin and prazosin as adjuncts to beta adrenoceptor blockade in hypertension

“…Mean values for blood pressure, pulse rate, plasma renin activity, and body weight of 15 patients in the double-blind randomized crossover study < 0.01 activity by radioimmunoassay 14. Statistical analyses were made by Student's paired t test.Blood pressure responses in individual patients were graded by the method of Walker and coworkers 15. …”

Novel Hypotensive Agents from Verbesina caracasana. 8. Synthesis and Pharmacology of (3,4-Dimethoxycinnamoyl)-N-agmatine and Synthetic Analogues1

“…In this respect 10a, 16a, and 10b-e seem to be, in a clinical perspective, more suitable hypotensive (antihypertensive) drugs because of the lack, as compared with some natural analogues, of consistent positive inotropic (as G1 and G2), 20,22 respiratory, and chronotropic side effects (as G2 and G7). 22,23 Although this study has not been directed to investigate the action mechanisms of the tested guanidine compounds, it is likely, considering the results obtained with their natural analogues, [20][21][22][23] that they too are provided with multiple action mechanisms (as also found for other guanidine derivatives such as guanethidine 5 and guanabenz 6 ). Moreover, although a guanidine moiety is also shown by complex with nitric oxide (NO) synthase to have inhibitory activity [like L-NAME (nitroarginine methyl ester) and aminoguanidine], a similar mechanism is quite unlikely for our guanidine compounds, inducing, on the contrary, arterial vasodilation and slight positive inotropic effects (NO is known to induce vascular relaxation, to depress cardiac activity, and to be an antiarrhythmic agent).…”

Novel Hypotensive Agents from Verbesina caracasana. 6. Synthesis and Pharmacology of Caracasandiamide

“…A similar cisoid disposition, revealed by the high-field signal of the 3′-methoxy groups in the 1 H NMR spectrum, requires the two aromatic rings to be face to face. A strongly acidic hydrolysis (2 N H 2 SO 4 in MeOH) of 3 gave again prenylurea, prenylagmatine (4), and the methyl ester 5 (Chart 1). The chemical shift (δ 3.68) of the equivalent carbomethoxy groups in the 1 H NMR spectrum indicated that they do not face the aryl rings.…”

“…Synthetic derivatives of guanidine (e.g., guanethidine, guanabenz, and guanfacine 5 ) have been introduced in antihypertensive drug therapy for their ability to block adrenergic nerve activity through central and/or peripheral mechanisms. , Also pinacidil, an (arylamino)guanidine, is able to lower blood pressure, acting on arterial vasodilation.…”