A pharmacodynamic study of the alpha 2-adrenergic receptor antagonist ethoxyidazoxan in healthy volunteers.
Ethoxyidazoxan, a potent and highly selective alpha 2-adrenergic receptor antagonist, was administered intravenously to six healthy male volunteers in a double-blind, placebo-controlled, dose-rising design. Doses of 6 micrograms/kg and 8 micrograms/kg infused intravenously over 30 minutes produced significant elevations of plasma norepinephrine and body temperature and inhibited norepinephrine-induced platelet aggregation. Central activity was shown by reversal of the slowing of saccadic eye movements and an increase in saccade peak velocity at the higher dose. Modest increases in blood pressure were produced without change in heart rate. Ethoxyidazoxan was well tolerated, with slight changes in subjective alertness and sedation.
Coupland
N J
NJ
Psychopharmacology Unit, School of Medical Sciences, University of Bristol, England.
Bailey
J E
JE
Wilson
S J
SJ
Potter
W Z
WZ
Nutt
D J
DJ
D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D018592:Cross-Over Studies; D004146:Dioxanes / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012438:Saccades / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D010975:Platelet Aggregation Inhibitors; C065483:ethoxyidazoxan; D009638:Norepinephrine; D019329:Idazoxan