Platelet α2-adrenoreceptors in depression: a critical examination

Abstract

During the past decade, results from radioligand studies comparing platelet α(2)-adrenoreceptors in depressed patients and healthy volunteers have been inconsistent, especially when related to the known functional characteristics of these receptors. Despite the availability of radioligands for α(2)-adrenoreceptors, inherent methodological problems exist which make data from these studies difficult to interpret. The authors review the overall data from radioligand studies using [(3)H] clonidine and [(3)H] yohimbine of platelet α(2)-adrenoreceptors in depressed patients and healthy volunteers. Theoretical and methodological issues are critically examined in the light of recent findings. Finally, alternative strategies for studying α( 2)-adrenoreceptors in clinical populations are considered.

Potent, Selective Tetrahydro-β-carboline Antagonists of the Serotonin 2B (5HT2B) Contractile Receptor in the Rat Stomach Fundus

“…Among its multiple pharmacologic effects, yohimbine has been shown to antagonize 5HT-induced contractions in the rat stomach fundus, 22 an observation confirmed in our laboratory (-log K B ) 6.92), although it had 8-fold higher affinity as an R 2 adrenergic receptor antagonist (-log K B ) 7.77). 23,24 Our SAR studies employed functional data, utilizing the serotonin-induced contraction via the 5HT 2B receptor in rat stomach fundus smooth muscle strips in order to assess directly both affinity and antagonist activity of the newly synthesized ligands (Tables 1-5). We initiated such studies with a survey of several partial structural analogs of yohimbine (2-7), successively simplifying the molecule, to identify the key structural elements necessary for potent antagonism of 5HT 2B receptor-mediated contraction in the rat stomach fundus.…”