Receptor Subtypes and Endogenous Ligands: Rational Tools in the Search for Psychotropic Drugs

  • C. Braestrup
  • P. H. Andersen
Conference paper
Part of the Psychopharmacology Series book series (PSYCHOPHARM, volume 7)

Abstract

Relatively few new pharmacodynamic principles have been introduced in the late 1970s and early 1980s for the treatment of psychiatric disorders. This may reflect the type of experimental procedures used in the late 1960s and early 1970s, when animal models for psychiatric diseases were widely used for screening in the early discovery phases. These models, which were usually based on the performance of known efficacious psychotropic drugs, had a tendency to produce compounds which were similar to already known drugs. Today it seems that more rational approaches to the development of new CNS-active compounds have evolved in parallel with the explosive development in receptor research, and the results of these approaches are beginning to emerge.

Keywords

Dopamine Schizophrenia Cocaine Explosive Histamine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andersen PH, Braestrup C (1986) Evidence for different states of the dopamine D1 receptor: clozapine and fluperlapine may preferentially label an adenylate cyclase-coupled state of the D1 receptor. J Neurochem 47: 1822–1831PubMedCrossRefGoogle Scholar
  2. Andersen PH, Nielsen M (1987) Irradiation inactivation studies of the dopamine Dx receptor and dopamine-stimulated adenylate cyclase in rat striatum. Neurosci Lett 83: 167–172PubMedCrossRefGoogle Scholar
  3. Andersen PH, Gronvald FC, Jansen JAa (1985) A comparison between dopamine-estimulated adenylate cyclase and 3H-SCH 23390 binding in rat striatum. Life Sci 37: 1977–1983CrossRefGoogle Scholar
  4. Andersen PH, Nielsen EB, Grønvald FC, Braestrup C (1986) Some atypical neuroleptics inhibit [3H]SCH 23390 binding in vivo. Eur J Pharmacol 120: 143–144PubMedCrossRefGoogle Scholar
  5. Arnt J, Hyttel J, Meier E (1988) Inactivation of dopamine D-l or D-2 receptors differentially inhibits stereotypes induced dopamine agonists in rats. Eur J Pharmacol (in press)Google Scholar
  6. Arrang JM, Garbarg M, Lancelot JC, Lecomte JM, Pollard H, Robba M, Schunaek W, Schartz JC (1987) Highly potent and selective ligands for histamine H3-receptors. Nature 327: 117–123PubMedCrossRefGoogle Scholar
  7. Barbaccia ML, Costa E, Guidotti A (1988) Endogenous ligands for high-affinity recognition sites of psychotropic drugs. Annu Rev Pharmacol Toxicol 28: 451–476PubMedCrossRefGoogle Scholar
  8. Barnard EA, Darlison MG, Seeburg P (1987) Molecular biology of the GABAA receptor: the C. Braestrup and P. H. Andersen receptor/channel superfamily. Trends Neurosci 10: 502–509CrossRefGoogle Scholar
  9. Billard W, Ruperto V, Crosby G, Iorio LC, Barnett A (1984) Characterization of the binding of 3H-SCH 23390, a selective D1 receptor antagonist ligand, in rat striatum. Life Sci 35: 1885–1893PubMedCrossRefGoogle Scholar
  10. Birdsall NJM, Burgen ASV, Hulme EC (1978) The binding of agonists to brain muscarinic receptors. Mol Pharmacol 14: 723–736PubMedGoogle Scholar
  11. Bonner TI, Buckley NJ, Young AC, Brann MR (1987) Identification of a family of muscarinic acetylcholine receptor genes. Science 237: 527–532PubMedCrossRefGoogle Scholar
  12. Boulter J, Connolly J, Deneris E, Goldman D, Heinemann S, Patrick J (1987) Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family. Proc Natl Acad Sci USA 84: 7763–7767PubMedCrossRefGoogle Scholar
  13. Casey PJ, Gilman AG (1988) G protein involvement in receptor-effector coupling. Biol Chem 263: 2577–2580Google Scholar
  14. Drejer J, Honoré T (1988) Excitatory amino acid receptors. In: Elling K (ed) Glutamine and glutamate in mammals, vol 2. CRC, Boca Raton, pp 89–109Google Scholar
  15. Hammer R, Giachetti A (1982) Muscarinic receptor subtypes Ml and M2: biochemical and functional characterization. Life Sci 31: 2991–2998PubMedCrossRefGoogle Scholar
  16. Hammer R, Berrie CP, Birdsall NJ, Burgen AS, Hulme EC (1980) Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature 283: 90–92PubMedCrossRefGoogle Scholar
  17. Hulme EC, Burgen ASV, Birdsall NJM (1976) Interactions of agonists and antagonists with the muscarinic receptor. In: Worcel M, Vassort G (eds) Smooth muscle pharmacology and physiology. Inserm, Paris, pp 49–70Google Scholar
  18. Hyttel J (1983) SCH 23390 — the first selective dopamine D1 antagonist. Eur J Pharmacol 91: 153–154PubMedCrossRefGoogle Scholar
  19. Johansen PA, White FJ (1988) D1/D2 dopamine receptor interactions in the nucleus accumbens: the role of cAMP in electrophysiological responses. Soc Neurosci Abstr 14 (2): 931Google Scholar
  20. Kapocsi J, Somogyi GT, Ludvig N, Sefozo P, Harsin LG Jr, Woods RJ, Vizi ES (1987) Neurochemical evidence for two types of presynaptic alpha2-adrenoceptors. Neurochem Res 12: 141–147Google Scholar
  21. Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277: 93–96PubMedCrossRefGoogle Scholar
  22. Kelly E, Nahorski SR (1987) Endogenous dopamine functionally activates D-l and D-2 receptors in striatum. J Neurochem 49: 115–120PubMedCrossRefGoogle Scholar
  23. Lefkowitz RJ, Caron MG (1988) Adrenergic receptors as models for the study of receptors coupled to guanine nucleotide regulatory proteins. J Biol Chem 263: 4993–4996PubMedGoogle Scholar
  24. Morrow AL, Creese I (1986) Characterization of α1-adrenergic receptor subtypes in rat brain: a réévaluation of [3H]WB4104 and [3H]prazosin binding. Mol Pharmacol 29: 321–330PubMedGoogle Scholar
  25. Nielsen EB, Randrup K, Andersen PH (1989) Amphetamine discrimination: effects of dopamine receptor agonists. Eur J Pharmacol 160: 253–262PubMedCrossRefGoogle Scholar
  26. Schulz DW, Wyrick SD, Mailman RB (1984) 3H-SCH 23390 has the characteristics of a dopamine receptor ligand in the rat central nervous system. Eur J Pharmacol 106: 211–212Google Scholar
  27. Wachtel SR, Galloway MP, White F J (1988) D1 dopamine receptor stimulation enables the postsynaptic but not autoreceptor effects of D2 dopamine agonists. Soc Neurosci Abstr 14 (2): 1077Google Scholar
  28. Waddington JL, O’Boyle KM, Murray AM (1988) Stimulation of dopamine-sensitive adenylate cyclase and induction of grooming behaviour by new selective D-l agonists. Neurochem Int [Suppl 1] 13: F326Google Scholar
  29. White F J (1987) D-l dopamine receptor stimulation enables the inhibition of nucleus accumbens neurons by a D-2 receptor agonist. Eur J Pharmacol 135: 101PubMedCrossRefGoogle Scholar
  30. White FJ, Wachtel SR, Johansen PA, Einhorn LC (1987) Electrophysiological studies of the rat mesoaccumbens dopamine system: focus on dopamine receptor subtypes, interactions, and the effects of cocaine. In: Chiodo LA, Freeman AS (eds) Neurophysiology of dopaminergic systems — current status and clinical perspectives. Lakeshore, Grosse Pointe, pp 317–365Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • C. Braestrup
  • P. H. Andersen
    • 1
  1. 1.Pharmaceuticals R&DBagsværdDenmark

Personalised recommendations