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Effects of Desipramine Treatment upon Central Adrenoceptor Function in Normal Subjects

Published online by Cambridge University Press:  29 January 2018

T. H. Corn ,
C. Thompson  and
S. A. Checkley
T. H. Corn*
Affiliation:
Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF
C. Thompson
Affiliation:
Institute of Psychiatry
S. A. Checkley
Affiliation:
The Maudsley Hospital, Denmark Hill, London SE5 8AZ
*
∗Correspondence: Current address, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS.
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Summary

Six normal subjects were given clonidine infusions after 0, 1 and 3 weeks of treatment with desipramine (2 mg/kgm) and at 1 and 3 weeks after withdrawal from desipramine. The sedative and hypotensive effects of clonidine were inhibited after one and three weeks of desipramine treatment, and returned to normal after stopping treatment without any rebound increase. Such a time-course can be explained in terms of the acute effects of the drug, no adaptive changes at receptors need be invoked.

By contrast, the growth hormone response to clonidine tended to be increased after one week of desipramine, reduced after three weeks of treatment, and further reduced after discontinuation. Such a time-course is consistent with an adaptive down regulation at α2 adrenoceptors in response to their acute stimulation, due to noradrenaline re-uptake blockade.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 145 , Issue 2 , August 1984 , pp. 139 - 145
Copyright
Copyright © Royal College of Psychiatrists, 1984 

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References

Audiger, Y., Virion, A. & Schwartz, J. C. (1976) Stimulation of cerebral histamine H2 receptors by clonidine. Nature, 262, 307–8.Google Scholar
Beckett, P. J. & Finch, L. (1981) The α1 and α2 adrenoceptor involvement in the central cardiovascular action of clonidine in the conscious renal hypertensive cat. European Journal of Pharmacology, 82, 155–60.Google Scholar
Borkowski, K. R. & Finch, L. (1979) A comparison of the cardiovascular effects of centrally administered clonidine and adrenaline in anaesthetized rats. Journal of Pharmacy & Pharmacology, 31, 16–19.Google Scholar
Briant, R. H., Reid, J. C. & Dollery, C. T. (1973) Interaction between clonidine and desipramine in man. British Medical Journal, i, 522–3.Google Scholar
Cella, S. C., Picotti, G. B. & Muller, E. E. (1983) α2 adrenergic stimulation enhances growth hormone secretion in the dog. Life Sciences, 32, 2785–92.Google Scholar
Charney, D. S., Heninger, G. R. & Sternberg, D. E. (1982) Failure of chronic antidepressant treatment to alter growth hormone response to clonidine. Psychiatry Research, 6, 90.Google Scholar
Checkley, S. A. (1980) Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness. Psychological Medicine, 10, 35–53.Google Scholar
Checkley, S. A., Slade, A. P. & Shur, E. (1981a) Growth hormone and other responses to clonidine in patients with endogenous depression. British Journal of Psychiatry, 138, 51–5.CrossRefGoogle ScholarPubMed
Checkley, S. A., Slade, A. P., Shur, E. & Dawling, S. (1981b) A pilot study of the mechanism of action of desipramine. British Journal of Psychiatry, 138, 248–51.CrossRefGoogle ScholarPubMed
Checkley, S. A., Glass, I. B., Thompson, C., Corn, T. & Robinson, P. (1983) The GH response to clonidine in endogenous as compared to reactive depression. Psychological Medicine (submitted).CrossRefGoogle Scholar
Corn, T., Hoenig, A., Thompson, C., Bridges, P. K., Bartlett, J. R. & Checkley, S. A. (1984) A neuroendocrine study of stereotactic subcaudate frontal tractotomy. British Journal of Psychiatry, 144, 417–20.Google Scholar
Corn, T., Hale, A. S., Thompson, C., Bridges, P. R. & Checkley, S. A. (1984) A comparison of the GH responses to clonidine and apomorphine in the same endogenous depressed patients. British Journal of Psychiatry, (in press).Google Scholar
Cowen, P. J., Fraser, S., Grahame-Smith, D. G., Green, A. R. & Stanford, C. (1982) The effect of chronic antidepressant administration on β-adrenoceptor function in the rat pineal. British Journal of Pharmacology, 78, 89–96.CrossRefGoogle Scholar
Crews, F. T. & Smith, C. B. (1978) Presynaptic alpha-receptor subsensitivity after long term antidepressant treatment. Science, 202, 322–4.CrossRefGoogle ScholarPubMed
Crews, F. T. (1980) Potentiation of responses to adrenergic nerve stimulation in isolated rat atria during chronic tricyclic antidepressant treatment. Journal of Pharmacology and Experimental Therapeutics, 215, 143–9.Google Scholar
Delini-Stula, A., Baumann, P. & Buch, O. (1979) Depression of exploratory activity by clonidine in rats as a model for the detection of relative pre- and postsynaptic central noradrenergic receptor selectivity of β-adrenolytic drugs. Naunyn-Schmiedeberg's Archives of Pharmacology, 307, 115–212.Google Scholar
Drew, G. M., Gower, A. J. & Marriott, A. S. (1979) Alpha adrenoceptors mediate clonidine induced sedation in rats. British Journal of Pharmacology, 67, 135–41.CrossRefGoogle Scholar
Eriksson, E., Eden, S. & Modigh, K. (1982) Up and down regulation of central post synaptic alpha2 receptors reflected in the growth hormone response to clonidine in reserpine pretreated rats. Psychopharmacology, 77, 327–31.Google Scholar
Finch, L. (1975) The central hypotensive action of clonidine and BAY 1470 in cats and rats. Clinical Science and Molecular Medicine, 48, 273–6s.Google Scholar
Finch, L., Harvey, C. A., Hicks, P. E. & Owen, D. A. A. (1978) Clonidine-induced hypotension: further evidence for a central interaction with histamine H2 receptor antagonists in the rat. Neuropharmacology, 17, 307–13.Google Scholar
Glass, I. B., Checkley, S. A., Shur, E. & Dawling, S. (1982) The effect of desipramine upon central adrenergic function in depressed patients. British Journal of Psychiatry, 141, 372–6.CrossRefGoogle ScholarPubMed
Gorka, L. & Zacny, E. (1981) The effect of single and chronic administration of imipramine on clonidine-induced hypothemia in the rat. Life Sciences, 28, 2847–54.Google Scholar
Haeusler, G. (1974) Clonidine-induced inhibition of sympathetic nerve activity; no indication for a central presynaptic or an indirect sympathomimetic mode of action. Naunyn Schmiedeberg's Archives of Pharmacology, 286, 97–111.CrossRefGoogle ScholarPubMed
Hamilton, T. C., Hunt, A. A. E. & Poyser, R. H. (1980) Involvement of central α2 adrenoceptors in the mediation of clonidine-induced hypotension in the cat. Journal of Pharmacy and Pharmacology, 32, 788–9.Google Scholar
Heydorn, W. E., Brunswick, D. J. & Frazer, A. (1982) Effect of treatment of rats with antidepressants on melatonin concentrations in the pineal glad and serum. Journal of Pharmacology and Experimental Therapeutics, 222, 534–43.Google Scholar
Isaac, L. (1981) Brain sites for the antihypertensive action of clonidine. In Psychopharmacology of Clonidine (eds. Lal H. and Fielding S.). New York: Alan R. Liss.Google Scholar
Kanof, P. & Greengard, P. (1978) Brain Histamine receptors as targets for antidepressant drugs. Nature, 272, 329–33.Google Scholar
Karppanen, H., Paakkari, I., Paakkari, P., Khotair, H. & Orma, A. L. (1976) Possible involvement of central histamine H2-receptors in the hypotensive effect of clonidine. Nature, 259, 587–8.Google Scholar
Kellar, K. J., Scascio, C. S., Bergstrom, D. A., Butler, J. A. & Ladarola, P. (1981) Electroconvulsive shock and reserpine: effects on β adrenergic. Journal of Neurochemistry, 37, 830–6.Google Scholar
Kobinger, W. & Pinchler, L. (1976) Centrally induced reduction in sympathetic tone—a post-synaptic α adrenoceptor-stimulating action of amidazolines. European Journal of Pharmacology, 40, 311–20.CrossRefGoogle Scholar
Kruhlich, L., Mayfield, M. A., Steele, M. K., McMillen, B. A., McCann, S. M. & Koenig, J. I. (1982) Differential effects of pharmacological manipulations at central α1 and α2 adrenergic receptors on the secretion of thyrotropin and growth hormone in male rats. Endocrinology, 110, 796–803.Google Scholar
Lovinger, R., Holland, J., Kaplan, S., Grummach, M. M., Boryczka, A. T., Shackleford, R., Salmon, J., Reid, I. A. & Ganońg, W. F. (1976) Pharmacological evidence for stimulation of growth hormone secretion by a central noradrenergic system in dogs. Neuroscience, 1, 443–50.CrossRefGoogle ScholarPubMed
McMillen, B. A., Warnack, W., German, D. C. & Shore, P. A. (1980) Effects of chronic desipramine treatment on rat brain noradrenergic responses to alpha adrenergic drugs. European Journal of Pharmacology, 61, 239–46.Google Scholar
McWilliam, J. R. & Meldrum, B. S. (1983) Noradrenergic regulation of growth hormone secretion in the baboon. Endocrinology, 112, 234–9.CrossRefGoogle ScholarPubMed
McWilliam, J. R., Meldrum, B. S. & Checkley, S. A. (1983) Changes in the sensitivity of the central a and β adrenergic systems during desmethylimipramine treatment as assessed by plasma growth hormone response in the baboon. Psychopharmacology, 80, 263–6.CrossRefGoogle ScholarPubMed
Maj, J., Baran, L., Sowinska, H. & Zielinski, M. (1975) The influence of cholinolytics on clonidine action. Polish Journal of Pharmacological Pharmacy, 27, 17–25.Google Scholar
Nomura, Y., Oki, R. & Segawa, T. (1980) Pharmacological characterization of central α-adrenoceptors which mediate clonidine-induced locomotor hypoactivity in the developing rat. Naunyn-Schmiedeberg's Archives of Pharmacology, 311, 41–4.Google Scholar
Pelayo, F., Dubocovich, M. L. & Langer, S. Z. (1980) Inhibition of neuronal uptake reduces the presynaptic effects of clonidine but not of a methylnoradrenaline on the stimulation-evoked release of 3H-noradrenaline from rat occipital cortex slices. European Journal of Pharmacology, 64, 143–55.Google Scholar
Pilc, A., Golembiowska-Nikitin, K. & Vetulani, J. (1979) Negligible binding of 3H-clonidine to Histamine H2 receptor. European Journal of Pharmacology, 56, 177–8.Google Scholar
Rockhold, R. W. & Caldwell, R. W. (1979) Effect of lesions of the nucleus tractus solitairie on the cardiovascular actions of clonidine in conscious rats. Neuropharmacology, 18, 347–56.Google Scholar
Rudolph, C. D., Kaplan, S. L., Ganong, W. F. (1980) Sites at which clonidine acts to affect blood pressure and the secretion of Renin, Growth Hormone and ACTH. Neuroendrocrinology, 31, 121–8.Google Scholar
Sakuma, M. & Knobil, E. (1970) Inhibition of endogenous growth hormone secretion by exogenous growth hormone infusion in the rhesus monkey. Endocrinology, 86, 890–4.Google ScholarPubMed
Schmitt, H., Schmitt, H. & Fernard, S. (1972) New evidence for an a adrenergic component in the sympathetic centres: centrally mediated decrease in sympathetic tone by L-DOPA and its antagonism by piperoxane and yohimbine. European Journal of Pharmacology, 17, 293–6.Google Scholar
Schmitt, H., Schmitt, H. & Fernard, S. (1977) Action of a adrenergic blocking drugs on the sympathetic centres and their interactions with the central sympathetic-inhibitory effect of clonidine. Arzneimittel-Forschung/Drug Research, 23, 40–5.Google Scholar
Sharma, J. N., Sandrew, B. B. & Wang, S. C. (1978) CNS site of action of clonidine induced hypotention: a microiontophoretic study of bulbar cardiovascular neurons. Brain Research, 191, 127–33.Google Scholar
Shur, E. & Checkley, S. A. (1982) Pupil studies in depressed patients: an investigation of the mechanism of action of desipramine. British Journal of Psychiatry, 140, 181–4.CrossRefGoogle ScholarPubMed
Siever, L. J., Uhde, T. W. & Murphy, D. L. (1982) Possible subsensitization of alpha2 adrenergic receptors by chronic monoamine oxidase inhibitor treatment in psychiatric patients. Psychiatry Research, 6, 293–302.Google Scholar
Slade, A. P. & Checkley, S. A. (1980) A neuro-endocrine study of the mechanism of action of ECT. British Journal of Psychiatry, 137, 217–21.Google Scholar
Snyder, S. H. Yamamura, H. J. (1977) Antidepressants and the muscarinic acetylcholine receptor. Archives of General, 34, 236–9.Google Scholar
Spyraki, C. & Fibiger, H. C. (1980) Functional evidence for subsensitivity of noradrenergic α2 receptors after chronic desipramine treatment. Life Sciences, 27, 1863–7.Google Scholar
Strombom, U. & Svensson, T. H. (1980) Clonidine: attenuation of sedative action by facilitated central noradrenergic neurotransmission. Journal of Neural Neurotransmission, 47, 29–39 Google Scholar
Sugrue, M. F. (1981) Effects of acutely and chronically administered antidepressants on the clonidine-induced decrease in rat brain MHPG content. Life Sciences, 28, 377–84Google Scholar
Svensson, T. H. & Usdin, T. (1978) Feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants: αreceptor mediation. Science, 202, 1089–91.CrossRefGoogle ScholarPubMed
Tadepalli, A. S. & Mills, E. (1978) Contribution of supracollicular structures of the brain to the central depression of cardiovascular function by clonidine. Journal of Pharmacology and Experimental Therapeutics, 203, 693–701.Google Scholar
Tang, S. W. Helmeste, D. M. & Stancer, H. C. (1978) The effect of acute and chronic desipramine and amitriptyline treatment on rat brain total 3 methoxy-4-hydroxyphenylglycol. Naunyn-Schmiedeberg's Archives of Pharmacology, 305, 207–11.Google Scholar
Tang, S. W. Helmeste, D. M. & Stancer, H. C. (1979) Interactions of antidepressants with clonidine on rat brain total 3-methoxy-4-hydroxyphenylglycol. Canadian Journal of Physiology and Pharmacology, 57, 435–7.Google Scholar
Thompson, C., Checkley, S. A., Corn, T., Franey, C. & Arendt, J. (1983) Down-regulation at pineal β-adrenoceptors in depressed patients treated with desipramine. Lancet, 1, 1101.CrossRefGoogle ScholarPubMed
Timmermans, P. B. M. W. M., Schoop, A. M. C., Kwa, H. Y. & van Zwieten, P. A. (1981) Characterization of the a adrenoceptors participating in the central hypotensive and sedative effects of clonidine using yohimbine, rauwolscine and coryanthine. European Journal of Pharmacology, 70, 7–15.Google Scholar
U'prichard, D. C., Greenberg, D. A., Sheehan, P. P. & Snyder, S. H. (1978) Tricyclic antidepressants: therapeutic properties and affinity for noradrenergic receptor binding sites in the brain. Science, 199, 197–8.Google Scholar
van Spanning, H. W. & van Zwieten, P. A. (1973) The interference of tricyclic antidepressants with the central hypotensive effect of clonidine. European Journal of Pharmacology, 24, 402–4.Google Scholar
van Zwieten, P. A. & Timmermans, P. B. M. W. M. (1978) The interaction between prazosin and clonidine. Clinical Science & Molecular Medicine, 55, 259s–61s.Google Scholar
Vogt, M. (1977) Histamine H2-Receptors in the brain and sleep produced by clonidine. European Journal of Pharmacology, 61, 331–443.Google ScholarPubMed
Warnke, E. & Hoefke, W. (1977) Influences of central pretreatment with β-hyroxydopamine on the hypotensive effect of clonidine. Arzneimittel-Forschung Drug Research, 27, 2311–13.Google Scholar
Zandberg, P., de Jong, W. & de Wied, D. (1979) Effect of catecholamine-receptor stimulating agents in blood pressure after local application solitarii of the medulla oblongata. European Journal of Pharmacology, 53, 43–56.Google Scholar
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