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α2‐Antagonist compounds and lipid mobilization: evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers
Author(s) -
GALITZKY J.,
TAOUIS M.,
BERLAN M.,
RIVIÈRE D.,
GARRIGUES M.,
LAFONTAN M.
Publication year - 1988
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1988.tb01272.x
Subject(s) - yohimbine , endocrinology , medicine , lipolysis , propranolol , chemistry , idazoxan , pharmacology , antagonist , prazosin , adipose tissue , receptor
. Investigations were carried out to analyse the interactions of α 2 ‐antagonists (yohimbine, idazoxan, SK & F‐86,466) with human fat cell α 2 ‐adrenoceptors. All the α 2 ‐antagonists enhanced the lipolytic potencies of epinephrine with an order of potency: yohimbine > idazoxan > SK & F‐86,466; the same order was also found in 3 H‐yohimbine competition studies on human fat cell membranes. The most potent agent, yohimbine, was administered orally in humans to define the conditions of appearance and the time‐course of a putative lipid‐mobilizing action. Oral yohimbine administration (0·2 mg kg ‐1 ) elevated plasma glycerol and non‐esterified fatty acids in fasting healthy subjects without significant action on heart rate or blood pressure during the time‐course of the experiment. The lipid‐mobilizing action of yohimbine was reinforced during physical exercise, completely suppressed after a meal and partially blocked by administration of propranolol (0·5 mg kg ‐1 ; 60 min before yohimbine). Plasma norepinephrine concentrations were increased (40–50%) after oral yohimbine administration. The rise in plasma catecholamine concentration elicited by yohimbine was not modified by propranolol treatment. The lipid‐mobilizing effect of yohimbine could be attributable to: (i) the increase in synaptic norepinephrine with a resultant increment in lipolysis by β‐adrenergic agonism; (ii) a decrease in α 2 ‐adrenoceptor stimulation of human fat cell α 2 ‐adrenoceptors; (iii) a blockade of presynaptic α 2 ‐adrenoceptors. The use of highly selective α 2 ‐antagonists will allow investigations into α 2 ‐adrenoceptors, which may represent a novel locus for pharmacological intervention in lipid‐mobilization strategies. It is questioned whether α 2 ‐antagonists would be useful in treatment or catecholamine‐refractoriness and obesity.