Cardiovascular, neuroendocrine, and sedative responses to four graded doses of clonidine in a placebo-controlled study.
Effects of four doses of the alpha 2-receptor agonist clonidine (CLO) (0.25, 0.5, 1, and 2 micrograms/kg IV) and placebo were studied in seven healthy men who volunteered in a double-blind randomized design in order to delineate possible presynaptic and postsynaptic components in the mechanism of action of CLO. Blood pressure, heart rate, plasma noradrenaline (NOR), plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma growth hormone (GH), and subjective sedation were monitored for a period of 1 hr following infusion of CLO. NOR and MHPG were also analyzed in urine, collected at 1 and 4 hr after the infusions. Dose-dependent decrements were observed in systolic and diastolic blood pressure and plasma NOR levels, and dose-dependent increases in subjective sedation and plasma GH. CLO did not influence plasma MHPG levels, whereas only urinary MHPG excretion was reduced 4 hr after infusion of 2 micrograms/kg CLO. Because no obvious differences between dose-response relations of plasma NOR (believed to be a presynaptic and peripheral effect), blood pressure (believed to be mainly a central presynaptic and postsynaptic effect), and subjective sedation (believed to be a central and probably postsynaptic effect) were observed, our results do not provide simple parameters to discern the multiple mechanisms of action of CLO. However, at a dose of 0.5 micrograms/kg CLO (a dose lower than that generally used) clear effects on plasma NOR, blood pressure, and sedation, but not on plasma GH (a central postsynaptic effect) or urinary MHPG (a presynaptic effect), were observed. When using CLO as a challenge test in psychiatric disorders, a design with 0.5 micrograms/kg CLO, in addition to the traditional 2 micrograms/kg CLO, may provide more information to characterize discrete abnormalities in the noradrenergic system at the level of the brainstem, the pituitary, or the peripheral sympathetic nervous system.
Tulen
J H
JH
Department of Psychiatry, University Hospital Rotterdam Dijkzigt, The Netherlands.
van de Wetering
B J
BJ
Kruijk
M P
MP
von Saher
R A
RA
Moleman
P
P
Boomsma
F
F
van Steenis
H G
HG
Man in 't Veld
A J
AJ
D000328:Adult; D001794:Blood Pressure; D002395:Catecholamines / Q000032:analysis / Q000652:urine; D002853:Chromatography, Liquid; D003000:Clonidine / Q000032:analysis / Q000097:blood; D004311:Double-Blind Method; D013006:Growth Hormone / Q000032:analysis* / Q000097:blood; D006339:Heart Rate; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000032:analysis / Q000097:blood; D009638:Norepinephrine / Q000032:analysis / Q000097:blood; D015990:Placebo Effect
D002395:Catecholamines; D008734:Methoxyhydroxyphenylglycol; D013006:Growth Hormone; D003000:Clonidine; D009638:Norepinephrine