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The Effect of Mianserin on Alpha-2 Adrenergic Receptor Function in Depressed Patients

Published online by Cambridge University Press:  29 January 2018

Dennis S. Charney ,
George R. Heninger  and
David E. Sternberg
Dennis S. Charney
Affiliation:
Department of Psychiatry, Connecticut Mental Health Center, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA
George R. Heninger
Affiliation:
Department of Psychiatry, Connecticut Mental Health Center, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA
David E. Sternberg
Affiliation:
Falkirk Hospital, Central Valley, NY 10917, USA
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Summary

Recent clinical investigations have shown that long term treatment with the tricyclic antidepressants desipramine and amitriptyline reduces the sensitivity of the alpha-2 adrenergic autoreceptor. In order to determine whether the tetracyclic antidepressant mianserin also has this action, the effect of clonidine, an alpha-2 adrenergic receptor agonist, on plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenlethyleneglycol (MHPG), blood pressure, and patient-rated sedation were measured in fifteen depressed patients before and during mianserin treatment. Postsynaptic alpha-2 adrenergic receptor function was assessed by measuring the growth hormone response to clonidine before and during treatment. Mianserin had little or no effect on the ability of clonidine to lower plasma MHPG and blood pressure, and to increase sedation and growth hormone secretion. The findings of this investigation indicates that long term mianserin treatment does not produce significant subsensitivity of the alpha-2 adrenergic receptor and suggests that a reduction in alpha-2 adrenergic autoreceptor sensitivity is not a necessary action for all effective antidepressant treatments.

Type
Papers
Information
The British Journal of Psychiatry , Volume 144 , Issue 4 , April 1984 , pp. 407 - 416
Copyright
Copyright © 1984 The Royal College of Psychiatrists 

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References

Anden, N. E., Grobowski, M. & Strombom, U. (1976) Different alpha-adrenoceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn-Schmiedeberg's Archives of Pharmacology, 292, 43–52.Google ScholarPubMed
Baumann, P. A. & Maitre, L. (1977) Blockade of presynaptic alpha-receptors and of amine reuptake in the rat brain by the antidepressant mianserin. Naunyn-Schmiedeberg's Archives of Pharmacology, 300, 31–7.Google Scholar
Cedarbaum, J. M. & Aghajanian, G. K. (1976) Noraadrenergic neurons of the locus coeruleus: inhibition of epinephrine and activation by the alpha-antagonist piperoxane. Brain Research, 112, 413–9.Google Scholar
Cedarbaum, J. M. & Aghajanian, G. K. (1977) Catecholamine receptors on locus coeruleus neurons: Pharmacological characterization. European Journal of Pharmacology, 44, 375–85.Google ScholarPubMed
Cerrito, F. & Raiteri, M. (1981) Supersensitivity of central noradrenergic presynnaptic autoreceptors following chronic treatment with the antidepressant mianserin. European Journal of Pharmacology, 70, 425–6.Google Scholar
Charney, D. S., Heninger, G. R & Sternberg, D. E. (1983) Alpha-2 adrenergic receptor sensitivity and the mechanism of action of antidepressant therapy: the effect of long term amitriptyline therapy. British Journal of Psychiatry, 142, 265–75.Google Scholar
Charney, D. S., Heninger, G. R, Sternberg, D. E. (1982b) Assessment of alpha-2 adrenergic autoreceptor function in humans: effects of oral yohimbine. Life Sciences, 30, 2033–41.Google Scholar
Charney, D. S., Heninger, G. R & Sternberg, D. E. (1982c) Failure of chronic antidepressant treatment to alter growth hormone response to clonidine. Psychiatry Research, 7, 135–8.Google Scholar
Charney, D. S., Heninger, G. R, Sternberg, D. E., Hafstad, K. M., Giddings, S. & Landis, D. H. (1982a) Adrenergic receptor sensitivity in depression: effects of clonidine in depressed patients and healthy subjects. Archives of General Psychiatry, 39, 290–4.Google Scholar
Charney, D. S., Heninger, G. R, Sternberg, D. E., Redmond, D. E., Leckman, J. F., Maas, J. W. & Roth, R. H. (1981b) Presynaptic adrenergic receptor sensitivity in depression: the effects on long term desipramine treatment. Archives of General Psychiatry, 38, 1334–40.CrossRefGoogle ScholarPubMed
Charney, D. S., Menkes, D. B. & Heninger, G. R. (1981a) Receptor sensitivity and the mechanism of action of antidepressant treatment. Implications for the etiology and therapy of depression. Archives of General Psychiatry, 38, 1160–80.Google Scholar
Checkley, S. A., Slade, A. P., Shur, E. & Dawling, S. (1981a) A pilot study of the mechanism of action of desipramine. British Journal of Psychiatry, 138, 248–51.Google Scholar
Checkley, S. A., Slade, A. P., Shur, E. & Dawling, S. (1981b) Growth hormone and other responses to clonidine in patients with endogenous depression. British Journal of Psychiatry, 138, 51–5.Google Scholar
Clements-Jewery, S. (1978) The development of cortical beta-adrenoceptor subsensitivity in the rat by chronic treatment with trazadone, doxepine and mianserin. Neuropharmacology, 17, 779–81.Google Scholar
Clineschmidt, B. V., Flataker, L. M., Faison, E. & Holmes, R. (1979) An in vivo model for investigating alpha-1 and alpha-2 receptors in the CNS: studies with mianserin. Archives Internationales de pharmacodynamie et de Therapie, 242, 59–76.Google Scholar
Dekirmenjian, H. & Maas, J. W. (1974) 3-Methoxy-4-hydroxyphenethyleneglycol in plasma. Clinical Chimica Acta, 52, 203–210.Google Scholar
Delini-Stula, A., Baumann, P. & Buch, D. (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 alpha-adrenolytic drugs. Naunyn-Schmiedeberg's Archives of Pharmacology, 307, 115–22.Google Scholar
Drew, G. M., Gower, H. J. & Marriot, A. S. (1979) Alpha-2 adrenoceptors mediate clonidine induced sedation in the rat. British Journal of Pharmacology, 67, 133.CrossRefGoogle ScholarPubMed
Dumbrille-Ross, A., Tang, S. W. & Coscina, D. V. (1981) Differential binding of 3H-imipramine and 3H-mianserin in rat cerebral cortex. Life Science, 29, 2049–58.Google ScholarPubMed
Elsworth, J. D., Redmond, D. E. & Roth, R. H. (1982) Plasma and cerebrospinal fluid 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) as indices of brain norepinephrine metabolism in primates. Brain Research, 235, 115–24.Google Scholar
Engberg, G. &. Svensson, T. H. (1980) Mianserin: Direct activation of brain norepinephrine neurons by blocking alpha-2 receptors. Communications in Psychopharmacology, 4, 233–39.Google Scholar
Fludder, J. M. & Leonard, B. E. (1979) Chronic effects of mianserin on noradrenaline metabolism in the rat brain: Evidence for a presynaptic alphz-adrenolytic action in vivo. Psychopharmacology, 64, 329–32.Google Scholar
Fludder, J. M. & Leonard, B. E. (1978) Interaction between mianserin and clonidine in rat brain in vivo. Communication in Psychopharmacology, 2, 487–90.Google Scholar
Glass, I. B., Checkley, S. A., Shur, E. & Dawling, S. (1982) The effect of desipramine on central adrenergic function in depressed patients. British Journal of Psychiatry, 141, 372–6.Google Scholar
Goodlet, I., Mireylees, S. E. & Sugrue, M. F. (1977) Effects of mianserin, a new antidepressant, on the vitro and in vivo uptake of monoamines. British Journal of Pharmacology, 61, 307–13.CrossRefGoogle ScholarPubMed
Hall, H. & Ogren, S. O. (1981) Effects of antidepressant drugs on different receptors in the brain. European Journal of Pharmacology, 7, 393–407.Google Scholar
Hamilton, M. (1960) A rating scale for depression. Journal of Neurology and Neurosurgery and Psychiatry, 23, 56–62.Google Scholar
Harper, B. & Hughes, I. E. (1979) Presynaptic alpha-adrenoeptor blocking properties among tri- and tetracyclic antidepressant drugs. British Journal of Pharmacology, 67, 511–7.CrossRefGoogle Scholar
Holmberg, G. & Gershon, S. (1961) Autonomic and psychic effects of yohimbine hydrochloride. Psychopharmacology, 2, 93–116.Google Scholar
Jones, R. S. G. (1980) Enhancement of 5-hydroxytryptamine-induced behavioral effects following chronic administration of antidepressant drugs. Psychopharmacology, 69, 307–11.Google Scholar
Lang, W. J. & Gershon, S. (1963) Effects of psychoactive drugs on yohimbine induced responses in conscious dogs. Archives Internationales de pharmacodynamic et de Therapie, 142, 457–74.Google Scholar
Leckman, J. F., Maas, J. W., Redmond, D. E. & Heninger, G. R. (1980) Effect of oral clonidine on plasma 3-methoxy-4-hydroxyphenylethyleneglycol and diastolic blood pressure. European Journal of Pharmacology, 70, 111–20.Google Scholar
Maas, J. W., Hattox, S. E., Greene, N. M. & Landis, D. H. (1979) MHPG production by human brain in vivo . Science, 205, 1025–7.Google Scholar
Maas, J. W., Landis, H. & Dekirmenjian, H. (1976) The occurence of free vs. conjugated MHPG in nonhuman and human primate brain. Psychopharmacology Communciations, 2, 403–10.Google Scholar
Maggi, A., U'Prichard, D. C. & Enna, S. J. (1980) Differential effects of antidepressant treatment on brain monoamine receptors. European Journal of Pharmacology, 61, 91–8.Google Scholar
Maj, J., Mogilnicka, E. & Klimek, V. (1979) The effect of repeated administration of antidepressant drugs on the responsiveness of rats to catecholamine agonists. Journal of Neural Transmission, 44, 221–35.Google Scholar
Maj, J., Sowinski, H., Baran, L., Gancarczyk, L. et al, (1978) The central antiserotonin action of mianserin. Psychopharmacology, 59, 79–84.Google Scholar
Matussek, N., Ackenheil, M., Hippius, H., Muller, F., Shroder, T-TH, Schultes, H. & Wasilewski, B. (1980) Effects of clonidine on growth hormone release in psychiatric patients and controls. Psychiatry Research, 2, 25–36.Google Scholar
Mishia, R., Janowsky, A. & Sulser, F. (1980) Action of mianserin and zimelidine on the norepinephrine receptor coupled adenylate cyclase system in brain: subsensitivity without reduction in beta-adrenergic receptor binding. Neuropharmacology, 19, 983–7.Google Scholar
Mogilnicka, E. & Klimek, V. (1979) Mianserin, lanitracen, and amitriptyline withdrawal increases behavioural responses of rats to L-5-HTP. Journal of Pharmacology and Pharmaceutics, 31, 704–5.Google Scholar
Mogilnicka, E. & Przewlocka, B. (1981) Facilitated shock-induced aggression after chronic treatment with antidepressant drugs in the rat. Pharmacology, Biochemistry, and Behavior, 14, 129–32.Google Scholar
Pommier, Y., Andrejak, M., Mouille, H., Dabire, H. et al, (1982) Interaction between mianserin and clonidine at alpha-2 adrenoceptors. Naunyn-Schmiedeberg's archives of Pharmacology, 318, 288–94.Google Scholar
Robson, D. P., Antonaccio, M. J. Saelens, J. K. & Liebman, J. (1978) Antagonism by mianserin and classical alpha-adrenoceptor blocking drugs on some cardiovascular and behavioral effects of clonidine. European Journal of Pharmacology, 47, 431–42.Google Scholar
Rockhold, R. W. & Caldwell, R. W. (1980) Cardiovascular effects following clonidine microinjection into the nucleus tractus solitarii of the rat. Neuropharmacology, 19, 911–22.Google Scholar
Scatton, B., Zivkovic, B. & Dedek, J. (1980) Antidopaminergic properties of yohimbine. Journal of Pharmacology and Experimental Therapeutics, 215, 494–9.Google ScholarPubMed
Schlach, D. S. & Parker, M. L. (1964) A sensitive double antibody immunoassay for human growth hormone in plasma. Nature, 263, 1141–2.Google Scholar
Scuvee-Moreau, J. J. & Svensson, T. H. (1982) Sensitivity in vivo of central alpha-2 and opiate receptors after chronic treatment with various antidepressants. Journal of Neural Transmission, 54, 51–63.Google Scholar
Siever, L. J., Unde, T. W., Insel, T. R., Roy, B. F. & Murphy, D. L. (1982) Growth hormone response to clonidine unchanged by chronic clorgyline treatment. Psychiatry Research, 7, 139–43.Google Scholar
Strombom, U. & Svensson, T. H. (1980) Clonidine: attenuation of sedative action by facilitated central noradrenergic neurotransmission. Journal of Neural Transmission, 47, 29–9.Google Scholar
Sugrue, M. F. (1982) A study of the sensitivity of rat brain alpha-2 adrenoceptors during chronic antidepressant treatments. Naunyn-Schmniedeberg's Archives of Pharmacology, 320, 90–6.Google Scholar
Sugrue, M. F. (1980) The inability of chronic mianserin to block central alpha-2 adrenoceptors. Eurpean Journal of Pharmacology, 68, 377–80.Google Scholar
Tang, S. W., Helmeste, D. M. & Stancer, H. C. (1979) Interactions of antidepressants with clonidine on rat brain total 3-methoxy-4-hydroxyphenyglycol. Canadian Journal of Physiology and Pharmacology, 57, 435–7.Google Scholar
Tang, S. W. & Seeman, P. (1980) Effect of antidepressant drugs on serotonergic and adrenergic receptors. Naunyn-Schmie-deberg's Archives of Pharmacology, 311, 255–61.Google ScholarPubMed
Terry, L. C. & Martin, J. B. (1981) Evidence for alpha-adrenergic regulation of episodic growth hormone and prolactin secretion in the undisturbed male rat. Endocrinology, 108, 1869–73.Google Scholar
Timmermans, P. B. M. W. M., Schoop, A. M. C. Kwa, H. Y. et al (1981) Characterization of alpha-adrenoceptors participating in the central hypotensive and sedative effects of clonidine using yohimbine, rauwolscine, and coryanthine. European Journal of Pharmacology, 70, 7–16.Google Scholar
Van Riezen, H. (1972) Differential central effects of the 5HT antagonists mianserin and cyproheptadine. Archives Internationales de Pharmacodynamic el de Therapie, 198, 256–69.Google Scholar
Whitaker, P. M. & Cross, A. J. (1980) 3H-mianserin binding in calf caudate: possible involvement of serotonin receptors in antidepressant drug action. Biochemical Pharmacology, 29, 2709–12.Google Scholar
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