Synthesis of 3-amino-2-(3-indolyl)propanol and propanoate derivatives and preliminary cardiovascular evaluation in rats.
A series of tryptamine analogues has been prepared and tested for their 5-HT1 receptor agonist properties. The incorporation of an alkoxy group at the C-5 position of the indole nucleus resulted in a short-lived and dose-dependent immediate antihypertensive and bradycardic response in anaesthetized spontaneously hypertensive rats (SHR). In addition, a carbomethoxy function at the beta-position of the side-chain of the tryptamines significantly increased the mean resting arterial blood pressure (MAP) in pithed rats and also produced contraction of the canine basilar artery in a dose-dependent fashion. Structure-activity relationships (SAR) suggest that the 5-alkoxy group is an important pharmacophore in the production of the antihypertensive effect and that the introduction of a hydroxymethylene group on the side-chain, instead of the carbomethoxy group, changed the receptor affinity profile.
Pérez-Alvarez
V
V
Departamento de Farmacología y Toxicología, Instituto Politécnico Nacional, México D.F., Mexico.
Morales-Ríos
M S
MS
Hong
E
E
Joseph-Nathan
P
P
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D008735:5-Methoxytryptamine; C033600:indorenate