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Antidepressants and components of the beta adrenoceptor system: studies on zimelidine

  • R. Klysner
  • A. Geisler
  • P. Andersen

Abstract

Treatment of rats with a number of antidepressants for one to several weeks leads to a decrease in the density of beta adrenoceptors in the cerebral cortex and other brain regions (Bergstrom and Kellar, 1979; Maggi et al., 1980). This reduction is accompanied by a concomitant decrease in the beta adrenoceptormediated cyclic AMP accumulation (Vetulani et al., 1976; Wolfe et al., 1978). Similar beta adrenoceptor alterations are also evoked by other antidepressant treatments. Thus, treatment with electro-convulsive therapy and monoamine oxidase inhibitors also induce beta adrenoceptor down-regulation (Gillespie et al., 1979; Sellinger-Barnette et al., 1980). The antidepressant treatments, however, have to be administered for a clinically relevant period of time before the changes are observable, whereas a single treatment does not change the number of beta adrenoceptors nor the associated cyclic AMP accumulation (Sarai et al., 1978; Vetulani et al., 1976; Wolfe et al., 1978).

Keywords

Antidepressant Treatment Antagonist Binding Agonist Binding Site Beta Adrenoceptor Agonist Beta Adrenoceptors 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Aberg-Wistedt, A., Jostell, K.-G., Ross, S. and Westerlund, D. (1981). Effects of zimelidine and desipramine on serotonin and noradrenaline uptake mechanisms in relation to plasma concentrations and to therapeutic effects during treatment of depression. Psychopharmacology, 74, 297–305CrossRefPubMedGoogle Scholar
  2. Bergstrom, D.A. and Kellar, K.J. (1979). Adrenergic and serotonergic receptor binding in rat brain after chronic desmethylimipramine treatment. J. Pharmacol. Exp. Ther., 209, 256–61PubMedGoogle Scholar
  3. Bylund, D.B. and Snyder, S.H. (1976). Beta adrenergic receptor binding in membrane preparations from mammalian brain. Mol. Pharmacol., 12, 568–80PubMedGoogle Scholar
  4. Citri, Y. and Schramm, M. (1980). Resolution, reconstitution and kinetics of the primary action of a hormone receptor. Nature, 287, 297–300CrossRefPubMedGoogle Scholar
  5. Coppen, A., Rama Rao, V.A., Swade, C. and Wood, K. (1979). Zitmelidine: a therapeutic and pharmacokinetic study in depression. Psychopharmacology, 63, 199–202CrossRefPubMedGoogle Scholar
  6. Crews, F.T., Paul, S.M. and Goodwin, F.K. (1981). Acceleration of beta-receptor desensitization in combined administration of antidepressants and phenoxybenzamine. Nature, 290, 787–9CrossRefPubMedGoogle Scholar
  7. Extein, I., Tallman, J., Smith, C.O and Goodwin, F.K. (1979). Changes in lymphocyte beta-adrenergic receptors in depression and in mania. Psychiatry Res., 1, 191–7CrossRefPubMedGoogle Scholar
  8. Frazer, A., Hess, M.E., Mendels, J., Gable, B., Kunkel, E. and Bender, A. (1978). Influence of acute and chronic treatment with desmethylimipramine on catecholamine effects in the rat. J. Pharmacol. Exp. Ther., 206, 311–19PubMedGoogle Scholar
  9. Geisler, A., Klysner, R., Thams, P. and Christensen, S. (1977). A simple and inexpensive protein binding assay for cyclic AMP in biological materials. Acta Pharmacol. Toxicol., 40, 356–68.CrossRefGoogle Scholar
  10. Gillespie, D.D., Manier, D.H. and Sulser, F. (1979). Electroconvulsive treatment: rapid subsensitivity of the norepinephrine receptor coupled adenylate cyclase system in brain linked to down-regulation of beta-adrenergic receptors. Commun. Psychopharmacol., 3, 191–5PubMedGoogle Scholar
  11. Klysner, R. amd Geisler, A. (1983). Effect of REM sleep deprivation on beta-adrenergic receptors in rat brain. Submitted for publicationGoogle Scholar
  12. Laursen, H., Klysner, R. and Geisler, A. (1977). Adenylate cyclase activity in corpus striatum of rats with porto-caval anastomosis. Acta Physiol. Scand., 100, 282–7CrossRefPubMedGoogle Scholar
  13. Lerer, B., Ebstein, R,P, and Belmaker, R.H. (1981). Subsensitivity of human beta-adrenergic adenylate cyclase after salbutamol treatment of depression. Psychopharmacology, 75, 169–72CrossRefPubMedGoogle Scholar
  14. Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951). Protein measurement with the folin phenol reagent. J. Biol. Chem., 193, 265–75PubMedGoogle Scholar
  15. Maggi, A., U’Prichard, D.C. and Enna, S.J. (1980). Differential effects of antidepressant treatment on brain monoaminergic receptors. Eur. J. Pharmacol., 61, 91–8CrossRefPubMedGoogle Scholar
  16. Mishra, R., Janowsky, A. and Sulser, F. (1979). Subsensitivity of the norepinephrine receptor-controlled adenylate cyclase system in brain: effects of nisoxetine versus fluoxetine. Eur. J. Pharmacol., 60, 379–82CrossRefPubMedGoogle Scholar
  17. Mishra, R., Janowsky, A. and 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, 983–7CrossRefPubMedGoogle Scholar
  18. Mogilnicka, E., Arbilla, S., Depoortere, H. and Langer, S.Z. (1980). Rapid-eye-movement sleep deprivation decreases the density of 3H-dihydroalprenolol and 3H-imipramine binding sites in the rat cerebral cortex. Eur. J. Pharmacol., 65, 289–92CrossRefPubMedGoogle Scholar
  19. Pandey, G.N., Dysken, M.W., Garver, D.L. and Davis, J.M. (1979). Beta-adrenergic receptor function in affective illness. Am. J. Psychiatry, 136, 675–8CrossRefPubMedGoogle Scholar
  20. Reynolds, C.H. and Claxton, P.T.J. (1982). Inhibition of calmodulin-activated cyclic nucleotide phosphodiesterase: Multiple binding-sites for tricyclic drugs on calmodulin. Biochem. Pharmacol., 31, 419–21CrossRefPubMedGoogle Scholar
  21. Rosenblatt, J.E., Pert, C.B., Tall, J.F., Pert, A. and Bunney, W.E. (1979). The effect of imipramine and lithium on alpha-and beta-receptor binding in rat brain. Brain Res., 160, 186–91CrossRefPubMedGoogle Scholar
  22. Ross, S.B., Hall, H., Renyi, A.L. and Westerlund, D. (1981). Effects of zimelidine on serotonergic and noradrenergic neurons after repeated administration in the rat. Psychopharmacology, 72, 219–25CrossRefPubMedGoogle Scholar
  23. Sarai, K., Frazer, A., Brunswick, D. and Mendels, J. (1978). Desmethylimipramine-induced decrease in beta-adrenergic receptor binding in rat cerebral cortex. Biochem. Pharmacol., 27, 2179–81CrossRefPubMedGoogle Scholar
  24. Scatchard, G. (1949). The attraction of proteins for small molecules and ions. Ann. NY Acad. Sci., 51, 660–72CrossRefGoogle Scholar
  25. Schwabe, U., Miyake, M., Ohga, Y. and Daly, J.W. (1976). 4-(3-Cyclopentyloxy–4-methoxyphenyl)–2-pyrrolidone (ZK 62711): a potent inhibitor of adenosine cyclic 3’,5’-monophosphate phosphodiesterases in homogenates and tissue slices from rat brain. Mol. Pharmacol., 12, 900–10PubMedGoogle Scholar
  26. Sellinger-Barnette, M.M., Mendels, J. and Frazer, A. (1980). The effect of psychoactive drugs on beta-adrenergic receptor binding sites in rat brain. Neuropharmacology, 19, 447–54CrossRefPubMedGoogle Scholar
  27. Sethy, V.H. and Harris, D.W. (1981). Effect of norepinephrine uptake blocker on beta-adrenergic receptors of the rat cerebral cortex. Eur. J. Pharmacol., 75, 53–6CrossRefPubMedGoogle Scholar
  28. Sugrue, M.F. (1981). Effect of chronic antidepressant administration on rat frontal cortex alpha2- and beta-adrenoceptor binding. Br. J. Pharmacol., 74, 760P–1PGoogle Scholar
  29. Treiser, S. and Kellar, K. (1979). Lithium effects on adrenergic receptor supersensitivity in rat brain. Eur. J. Pharmacol., 58, 85–6CrossRefPubMedGoogle Scholar
  30. Vetulani, J., Stawarz, R.J., Dingell, J.V. and Sulser, F. (1976). A possible common mechanism of action of antidepressant treatments. Naunyn-Schmiedeberg’s Arch. Pharmacol., 293, 109–14CrossRefGoogle Scholar
  31. Vogel, G.W., Thurmond, A., Gibbons, P., Sloan, K., Boyd, M. and Walker, M. (1975). REM sleep reduction effects on depression syndromes. Arch. Gen. Psychiatry., 32, 765–77CrossRefPubMedGoogle Scholar
  32. Wiech, N.L. and Ursillo, R.C. (1980). Acceleration of desipramine-induced decrease of rat corticocerebral beta-adrenergic receptors by yohimbine. Commun. Psychopharmacol., 4, 95–100PubMedGoogle Scholar
  33. Wolfe, B.B., Harden, T.K., Sporn, J.R. and Molinoff, P.B. (1978). Presynaptic modulation of beta-adrenergic receptors in rat cerebral cortex after treatment with antidepressants. J. Pharmacol. Exp. Ther., 207, 446–57PubMedGoogle Scholar

Copyright information

© The contributors 1983

Authors and Affiliations

  • R. Klysner
    • 1
  • A. Geisler
    • 1
  • P. Andersen
    • 1
  1. 1.Department of PharmacologyUniversity of CopenhagenJuliane Maries vej 20Denmark

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