Skip to main content
SpringerLink
Log in
Book cover

Clinical Pharmacology in Psychiatry pp 288–300Cite as

Palgrave Macmillan

Antidepressants: effects on histaminic and muscarinic receptors

  • Chapter

Abstract

Antidepressant drugs of many chemical classes are antagonists of several different types of neurotransmitter receptors. Among the first known of these receptor interactions were the antagonisms of histamine H1 and muscarinic acetylcholine receptors. In fact, the first antidepressant, imipramine hydrochloride, was originally synthesized for use as an antihistamine (Kuhn, 1970). More recently, antidepressants have been shown, in addition, to be antagonists in vitro of histamine H2, α1-adrenergic, α2-adrenergic and serotonergic receptors. This paper will present the evidence that antidepressants antagonize histamine H1, histamine H2 and muscarinic acetylcholine receptors in brain and elsewhere. In addition the relevance of these data for the treatment of depression and other diseases will be discussed.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Atkinson, J. and Ladinsky, H. (1972). A quantitative study of the anticholinergic action of several tricyclic antidepressants on the rat isolated fundal strip. Br. J. Pharmacol., 48, 519–24

    Article  Google Scholar 

  • Bluhm, R.E. and Koller, W.C. (1981). Anticholinergic abuse — when to suspect it, what to do about it. Drug Ther., 11, 150–5

    Google Scholar 

  • Bohman, T., Myren, J., Flaten, O. and Schrumpf, E. (1980). The effect of trimipramine, cimetidine, and atropine on gastric secretion. Scand. J. Gastroent., 15, 177–82

    Article  CAS  PubMed  Google Scholar 

  • Brimblecombe, R.W. and Green, D.M. (1967). Central effects of imipramine-like antidepressants in relation to their peripheral anticholinergic activity. Int. J. Neuropharmacol., 6, 133–42

    Article  CAS  Google Scholar 

  • Burkard, W.P. (1978). Histamine H2-receptor binding with 3H-cimetidine in brain. Eur. J. Pharmacol., 50, 449–50

    Article  CAS  PubMed  Google Scholar 

  • Cheng, Y.-C. and Prusoff, W.H. (1973). Relationship between the inhibition constant (K I) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol., 22, 3099–108

    Article  CAS  PubMed  Google Scholar 

  • Davis, K.L., Berger, P.A., Hollister, L.E. and Barchas, J.D. (1978). Minireview: cholinergic involvement in mental disorders. Life Sci., 22, 1865–72

    Article  CAS  PubMed  Google Scholar 

  • Devoto, P., Marchisio, A.M., Carboni, E. and Spano, P.F. (1980). Detection of 3H-cimetidine specific binding in rat anterior pituitary. Eur. J. Pharmacol., 63, 91–3

    Article  CAS  PubMed  Google Scholar 

  • El-Fakahany, and Richelson, E. (1983). Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br. J. Pharmacol., 78, 97–102

    PubMed Central  CAS  PubMed  Google Scholar 

  • Figge, J., Leonard, P. and Richelson, E (1979). Tricyclic antidepressants: potent blockade of histamine H1 receptors of guinea pig ileum. Eur. J. Pharmacol., 58, 479–83

    Article  CAS  PubMed  Google Scholar 

  • Golds, P.R., Przyslo, F.R. and Strange, P.G. (1980). The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br. J. Pharmacol., 68, 541–9

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Green, J.P. and Maayani, S. (1977). Tricyclic antidepressant drugs block histamine H2 receptor in brain. Nature, 269, 163–5

    Article  CAS  PubMed  Google Scholar 

  • Hill, S.J., Emsons, P.C. and Young, J.M. (1978). The binding of [3H]-mepyramine to histamine H1 receptors in guinea-pig brain. J. Neurochem., 31, 997–1004

    Article  CAS  PubMed  Google Scholar 

  • Hill, S.J., Young, J.M. and Marrian, D.H. (1977). Specific binding of 3H-mepyramine to histamine H1 receptors in intestinal smooth muscle. Nature, 270, 361–3

    Article  CAS  PubMed  Google Scholar 

  • Hollenberg, M.D. and Cuatrecasas, P. (1979). Distinction of receptor from nonreceptor interactions in binding studies. In The Receptors, vol. 1 (ed. R.D. O’Brien), Plenum, New York, pp. 193–214

    Google Scholar 

  • Iizuka, H., Adachi, K., Halprin, K.M. and Levine, V. (1976). Histamine (H2) receptor-adenylate cyclase system in pig skin (epidermis). Biochim. Biophys. Acta, 150–7

    Google Scholar 

  • Janowsky, D.S., El-Yousef, M.K., Davis, J.M. and Sekerke, H.J. (1972). A cholinergic-adrenergic hypothesis of mania and depression. Lancet, ii, (Sept. 23), 632–35

    Article  Google Scholar 

  • Jefferson, J.W. (1979). Central nervous system toxicity of cimetidine: a case of depression. Am. J. Psychiatry, 136, 346

    Article  CAS  PubMed  Google Scholar 

  • Kanof, P.D. and Greengard, P. (1978). Brain histamine receptors as targets for antidepressant drugs. Nature, 272, 329–33

    Article  CAS  PubMed  Google Scholar 

  • Kendall, D.A, Ferkany, J.W. and Enna, S.J. (1980). Properties of 3H-cimetidine binding in rat brain membrane fractions. Life Sci., 26, 1293–302

    Article  CAS  PubMed  Google Scholar 

  • Kuhn, R. (1970). The imipramine story. In Discoveries in Biological Psychiatry, (ed. F.J. Ayd Jr and B. Blackwell), J.B. Lippincott Co., Philadelphia, pp. 205–17

    Google Scholar 

  • Mangla, J.C. and Pereira, M. (1982). Tricyclic antidepressants in the treatment of peptic ulcer disease. Arch. Intern. Med., 142, 273–5

    Article  CAS  PubMed  Google Scholar 

  • Munson, P.J. and Rodbard, D. (1980). LIGAND: a versatile computerized approach for characterization of ligand-binding systems. Anal. Biochem., 107, 220–39

    Article  CAS  PubMed  Google Scholar 

  • Petersen, R.C. and Richelson, E. (1982). Anticholinergic activity of imipramine and some analogs at muscarinic receptors of cultured mouse neuroblastoma cells. Psychopharmacology, 76, 26–8

    Article  CAS  PubMed  Google Scholar 

  • Psychoyos, S. (1981). Antidepressant inhibition of H1- and H2-histamine-receptor-mediated adenylate cyclase in [2-3H]-adenine-prelabeled vesicular preparations from guinea pig brain. Biochem. Pharmacol., 30, 2182–5

    Article  CAS  PubMed  Google Scholar 

  • Richelson, E. (1978a). Histamine H1 receptor-mediated guanosine 3’,5’-monophosphate formation by cultured mouse neuroblastoma cells. Science, 201, 69–71

    Article  CAS  PubMed  Google Scholar 

  • Richelson, E. (1978b). Tricyclic antidepressants block histamine H1 receptors of mouse neuroblastoma cells. Nature, 274, 176–7

    Article  CAS  PubMed  Google Scholar 

  • Richelson, E. (1979). Tricyclic antidepressants and histamine H1 receptors. Mayo Clinic Proc., 54, 669–74

    CAS  Google Scholar 

  • Richelson, E. (1983). Antimuscarinic and other receptor blocking properties of antidepressants. Mayo Clinic Proc., 58, 40–6

    CAS  Google Scholar 

  • Richelson, E. and Divinetz-Komero, S. (1977). B1ockade by psychotropic drugs of the muscarinic acetylcholine receptor in cultured nerve cells. Biol. Psychiatr., 12, 771–85

    CAS  Google Scholar 

  • Richelson, E., Prendergast, F.G. and Divinetz-Romero, S. (1978). Muscarinic receptor-mediated cyclic GMP formation by cultured nerve cells: ionic dependence and effects of local anesthetics. Biochem. Pharmacol., 27, 2039–48

    Article  CAS  PubMed  Google Scholar 

  • Rising, T.J., Norris, D.B., Warrander, S.E. and Wood, T.P. (1980). High affinity 3H-cimetidine binding in guinea-pig tissues. Life Sci., 27, 199–206

    Article  CAS  PubMed  Google Scholar 

  • Rosenfeld, G.C., Jacobson, E.D. and Thompson, W.J. (1976). Re-evaluation of the role of cyclic AMP in histamine-induced gastric acid secretion. Gastroenterology, 70, 832–5

    CAS  PubMed  Google Scholar 

  • Schwartz, J.-C., Garbarg, M. and Quach, T.T. (1981). Histamine receptors in brain as targets for tricyclic antidepressants. Trends Pharmacol. Sci., May, 122–5

    Google Scholar 

  • Shein, K. and Smith, S.E. (1978). Structure-activity relationships for the anticholinoceptor action of tricyclic antidepressants. Br. J. Pharmacol., 62, 567–71

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sullivan, T.J. (1982). Pharmacologic modulation of the whealing response to histamine in human skin: identification of doxepin as a potent in vivo inhibitor. J. Allergy Clin. Immunol., 69, 260–7

    Article  CAS  PubMed  Google Scholar 

  • Taylor, J.E. and Richelson, E. (1980). High-affinity binding of tricyclic antidepressants to histamine H1 receptors: fact and artifact. Eur. J. Pharmacol., 67, 41–6

    Article  CAS  PubMed  Google Scholar 

  • Taylor, J.E. and Richelson, E. (1981). Histamine receptors in neural tissue. In Neurotransmitter Receptors, pt 2, ser. B, vol. 10, of Receptors and Recognition, (ed. H.I. Yamamura and S. Enna), Chapman and Hall, London, pp. 71–100

    Chapter  Google Scholar 

  • Taylor, J.E. and Richelson, E. (1982). High affinity binding of [3H]doxepin to histamine H1 receptors in brain. Eur. J. Pharmacol., 78, 279–85

    Article  CAS  PubMed  Google Scholar 

  • Taylor, J.E., Yaksh, T.L. and Richelson, E. (1982). Histamine H1 receptors in the brain and spinal cord of the cat. Brain Res., 243, 391–4

    Article  CAS  PubMed  Google Scholar 

  • Tran, V.T., Chang, R.S.L. and Snyder, S.H. (1978). Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramine. Proc. Natl. Acad. Sci. USA, 75, 6290–4

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tran, V.T., Lebovitz, R., Roll, L. and Snyder, S.H. (1981). [3H]Doxepin interactions with histamine H1-receptors and other sites in guinea pig and rat brain homogenates. Eur. J. Pharmacol., 70, 501–9

    Article  CAS  PubMed  Google Scholar 

  • Tuong, M.D.T., Garbarg, M. and Schwartz, J.C. (1980). Pharmacological specificity of brain histamine H2-receptors differs in intact cells and cell-free preparations. Nature, 287, 548–51

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Psychiatry and Pharmacology, Mayo Foundation, 55905, Rochester, MN, USA

    Elliott Richelson

Authors
  1. Elliott Richelson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Clinical Pharmacology, Odense University, School of Medicine, Odense, Denmark

    Lars F. Gram

  2. Department of Psychiatry and Human Behavior, University of California, Irvine, California, USA

    Earl Usdin

  3. Department of Pharmacology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway

    Svein G. Dahl

  4. Department of Psychiatry, Odense University, School of Medicine, Odense, Denmark

    Per Kragh-Sørensen

  5. Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden

    Folke Sjöqvist

  6. L.E.R.S. Sythélabo, Paris, France

    Paolo L. Morselli

Copyright information

© 1983 The contributors

About this chapter

Cite this chapter

Richelson, E. (1983). Antidepressants: effects on histaminic and muscarinic receptors. In: Gram, L.F., Usdin, E., Dahl, S.G., Kragh-Sørensen, P., Sjöqvist, F., Morselli, P.L. (eds) Clinical Pharmacology in Psychiatry. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-06671-1_25

Download citation

Publish with us

Policies and ethics

Search

Navigation