RESUMEN

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.

Asunto(s)

5-Metoxitriptamina/análogos & derivados , 5-Metoxitriptamina/farmacología , Antihipertensivos/farmacología , Agonistas de Receptores de Serotonina/farmacología , 5-Metoxitriptamina/síntesis química , Animales , Antihipertensivos/síntesis química , Arteria Basilar/efectos de los fármacos , Arteria Basilar/fisiología , Presión Sanguínea/efectos de los fármacos , Estado de Descerebración , Perros , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Receptor de Serotonina 5-HT1D , Receptores de Serotonina/efectos de los fármacos , Receptores de Serotonina 5-HT1 , Agonistas de Receptores de Serotonina/síntesis química , Relación Estructura-Actividad