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Research Article| Volume 32, ISSUE 6, P485-500, September 15, 1992

Cardiovascular, neuroendocrine, and sedative responses to four graded doses of clonidine in a placebo-controlled study

  • J.H.M. Tulen
    Correspondence
    Address reprint requests to Dr. J. H. M. Tulen, Department of Psychiatry, University Hospital Rotterdam Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
    Affiliations
    From the Department of Psychiatry, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands

    Section Pathophysiology of Behavior, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands
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  • B.J.M. van de Wetering
    Affiliations
    From the Department of Psychiatry, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands
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  • M.P.C.W. Kruijk
    Affiliations
    From the Department of Psychiatry, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands
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  • R.A. von Saher
    Affiliations
    From the Department of Psychiatry, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands
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  • P. Moleman
    Affiliations
    From the Department of Psychiatry, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands
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  • F. Boomsma
    Affiliations
    Department of Internal Medicine I, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands
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  • H.G. van Steenis
    Affiliations
    Department of Clinical Neurophysiology, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands

    Section Pathophysiology of Behavior, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands
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  • A.J. Man in 't Veld
    Affiliations
    Department of Internal Medicine I, University Hospital Rotterdam Dijkzigt and Erasmus University Rotterdam, The Netherlands
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DOI:https://doi.org/10.1016/0006-3223(92)90217-N
Cardiovascular, neuroendocrine, and sedative responses to four graded doses of clonidine in a placebo-controlled study
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      Abstract

      Effects of four doses of the α2-receptor agonist clonidine (CLO) (0.25, 0.5, 1, and 2 μg/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 μg/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 μg/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 μg/kg CLO, in addition to the traditional 2 μg/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.
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      Article info

      Publication history

      Received in revised form: February 14, 1992
      Received: October 8, 1991

      Identification

      DOI: https://doi.org/10.1016/0006-3223(92)90217-N

      Copyright

      © 1992 Published by Elsevier Inc.

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