The cardiovascular pharmacological profiles of a series of novel indorenate analogs, including methyl 3-amino-(1H-indol-3-yl) propanoate hydrochloride and 3-amino-2-(1H-indol-3-yl)propanol oxalate 5-substituted analogs, were evaluated. The antihypertensive effects in anesthetized spontaneously hypertensive rats (SHR), direct action on blood pressure in the pithed rat preparation, on canine basilar artery vascular tone, and on the tension develop by rat aortic rings were assessed for the 5-methoxy, 5-fluor and 5 benzyloxy esters, and alcohol derivatives. 5-Alkoxytryptamine derivatives caused a short-lasting, dose-dependent immediate antihypertensive response, after which blood pressure returned to baseline. Ester derivatives induced both a significant long-lasting and dose-dependent increase in arterial blood pressure and elicited concentration-dependent contractions of the canine basilar artery. This last response was potently blocked by selective 5-HT 1B/1D antagonist GR 127935 (1 nM). Unlike the canine basilar artery, the rat aorta was almost insensitive to these alcohols and ester indorenate derivatives. Fluoro derivative 4 and the benzyloxy compounds 5 and 6 significantly inhibited phenylephrine-induced contractions of rat aorta rings at high concentrations. It is concluded that: 1) substitution of a 5-fluoro group instead of a 5-alcoxyl group increases affinity for 5-HT 1 subtype receptors; 2) the 5-alcoxy group is an important requirement for the antihypertensive effect; and 3) a β-carbomethoxy group in the lateral chain increases potency.