G. Dellemonache et al., NOVEL HYPOTENSIVE AGENTS FROM VERBESINA-CARACASANA .2. SYNTHESIS AND PHARMACOLOGY OF CARACASANAMIDE, Journal of medicinal chemistry, 36(20), 1993, pp. 2956-2963
Caracasanamide, one of the hypotensive agents isolated from Verbesina
caracasana, is a mixture of (Z)-1a and (E)-lb forms of )amino]-4-[(3-m
ethyl-2-butenyl)-guanidino]butane.1 The structure of (E)-caracasanamid
e (1b) was confirmed by high-yielding synthesis starting from N,N'-bis
(tert-butoxycarbonyl)-S-methylisothiourea. The water-soluble Z-form of
1a, assayed by iv route in anesthetized rats at doses ranging from 50
to 1600 mug/kg body weight, was found to decrease blood pressure, to
increase cardiac inotropism, respiratory frequency, and tidal volume,
and to induce a very slight and not significant tachycardia. Higher do
ses determined respiratory depression and, in some cases, consequent c
ardiac arrest. The compound was shown to affect cardiovascular functio
n by acting at the vascular level in inducing arterial vasodilation, b
y determining sympathetic hypotone through central neurogenic mechanis
ms, and by interacting with the cardiac beta1-adrenoreceptors. The res
piratory effects were independent of the cardiovascular ones. In lower
ing blood pressure, the compound was more potent than guanethidine and
not less potent than reserpine and papaverine. (Z)-Caracasanamide may
therefore be useful in the treatment of arterial hypertension of mode
rate degree.