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Putative agonists and antagonists at 5-HT1-like receptors

  • Wasyl Feniuk
  • Patrick P. A. Humphrey
Chapter
Part of the Developments in CardioCardiovascular Pharmacology of 5-Hydroxytryptamine book series (DICM, volume 106)

Abstract

There is little doubt that the classification of 5-hydroxytryptamine (5-HT) receptors has gone through a major transition over the last few years. Indeed it has been argued [1] that even the recent classification of Bradley and colleagues [2] is now outmoded. This need for change has largely arisen from some major advances from radioligand binding studies. However the acceptability and credibility of any receptor classification will be clearly dependent upon the selectivity and specificity of the agonists and antagonists which are used to define such receptor sites. It is perhaps worth emphasising, even at this early stage, that few selective and specific agonists and no specific antagonists are available in the area of 5-HT1 receptor research. Consequently the classification of 5-HT1 receptors, which has been so markedly influenced by the data generated from ligand binding studies, has on occasion, been met with scepticism [3]. Not withstanding such a criticism, certain new drug tools particularly agonists showing high degrees of selectivity [4] have recently become available. These may help unify a classification which seems in part to be based on ligand binding studies and in part on functional studies [1, 2].

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References

  1. 1.
    Fozard JR (1987): 5-HT: The enigma variations. Trends in Pharmacol Sci 100: 501–506.CrossRefGoogle Scholar
  2. 2.
    Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena PR (1986): Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacol25: 563–576.CrossRefGoogle Scholar
  3. 3.
    Leff P, Martin GR (1988): The classification of 5-hydroxytryptamine receptors. Med Res Rev8: 187 - 202.PubMedCrossRefGoogle Scholar
  4. 4.
    Humphrey PPA, Feniuk W, Perren MJ, Connor HE, Oxford AW, Coates IH, Butina D (1988): GR43175 a selective agonist for the 5-HT1-like receptor in dog isolated saphenous vein. Br J Pharmacol94: 1123–1132.PubMedCrossRefGoogle Scholar
  5. 5.
    Heuring RE, Peroutka SJ (1987): Characterisation of a novel 3H-5-hydroxytryptamine binding site in bovine brain membranes. J Neuroscience7: 894–903.Google Scholar
  6. 6.
    Peroutka SJ, Snyder SH (1979): Multiple serotonin receptors: Differential binding of [3H]-5-hydroxytryptamine, [3H] by lysergic acid diethylamide and [3H]-spiroperidol. Mol Pharmacol16: 687–699.PubMedGoogle Scholar
  7. 7.
    Leysen JE, Awouters F, Kennis L, Laduron PM, Vandenberk J, Janssen PAJ (1981): Receptor binding profile of R41468, a novel antagonist at 5-HT2 receptors. Life Sci28: 1015–1022.PubMedCrossRefGoogle Scholar
  8. 8.
    Hunt P, Oberlander C (1981): The interaction of indole derivatives with the serotonin receptor and non-dopaminergic circling behaviour. Adv Exp Med Biol133: 547–562.PubMedCrossRefGoogle Scholar
  9. 9.
    Middlemiss DN (1985): The putative 5-HT1, receptor agonist RU24969 inhibits the efflux of 5-hydroxytryptamine from rat frontal cortex slices by stimulation of the 5-HT autoreceptor. J Pharm Pharmac37: 434–437.CrossRefGoogle Scholar
  10. 10.
    Sills M, Wolfe BB, Frazer A (1984): Determination of selective and non selective compounds for the 5-HT1A and 5-HT1B receptor subtypes in rat frontal cortex. J Pharm Exp Ther231: 480–487.Google Scholar
  11. 11.
    Martin LL, Sanders-Bush E (1982): Comparison of the pharmacological characteristics of 5-HT1, binding sites with those of serotonin autoreceptors which modulate serotonin release. Naunyn-Schmiedeberg’s Arch Pharmacol321: 165–170.CrossRefGoogle Scholar
  12. 12.
    Cohen ML, Mason N, Wiley, KS, Fuller RW (1983): Further evidence that vascular serotonin receptors are of the 5-HT2 type. Biochem Pharmacol32: 567–570.PubMedCrossRefGoogle Scholar
  13. 13.
    Alper RH, Snider JM (1987): Activation of serotonin2 (5-HT2) receptors by quipazine increases arterial pressure and renin secretion in conscious rats. J Pharmacol Exp Ther243: 829–833.PubMedGoogle Scholar
  14. 14.
    Feniuk W, Humphrey PPA (1989): Mechanisms of 5-hydroxytryptamine-induced vasoconstriction, in: Fozard JR (ed), The Peripheral Actions of 5-Hydroxytryptamine. Oxford University Press.PubMedGoogle Scholar
  15. 15.
    Pedigo NW, Yamamura HI, Nelson DL (1981): Discrimination of multiple [3H]-5- hydroxytryptamine binding sites by the neuroleptic spiperone in rat brain. J Neurochem36: 220–226.PubMedCrossRefGoogle Scholar
  16. 16.
    Gozlan H, El-Mestikawy S, Picket L, Glowinsky J, Hammon M (1983): Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT. Nature (Lond) 305: 140 - 142.Google Scholar
  17. 17.
    Middlemiss DN, Fozard JR (1983): 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT,-recognition site. Eur J Pharmacol 90:151–153.CrossRefGoogle Scholar
  18. 18.
    Crist J, Suprenant A (1987): Evidence that 8-Hydroxy-2-(n-propylamino)-tetralin (8-OH-DPAT) is a selective α2-adrenoceptor antagonist on guinea-pig submucous neurones. Br J Pharmacol92: 341–347.PubMedCrossRefGoogle Scholar
  19. 19.
    Pazos A, Hoyer D, Palacios JM (1984): The binding of serotonergic ligands to the porcine choroid plexus: Characterisation of a new type of serotonin recognition site. Eur J Pharmacol106: 539–546.PubMedCrossRefGoogle Scholar
  20. 20.
    Fozard JR, Mir AK, Middlemiss DN (1987): Cardiovascular response to 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) in the rat: Site of action and pharmacological analysis. J Cardiovasc Pharmacol9: 328–347.PubMedCrossRefGoogle Scholar
  21. 21.
    Di Francesco GF, Petty AM, Fozard JR (1988): Antihypertensive effects of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in conscious dogs. Eur J Pharmacol147: 287–290.PubMedCrossRefGoogle Scholar
  22. 22.
    Ramage AG, Fozard JR (1987): Evidence that the putative 5-HT1A receptor agonists, 8-OH-DPAT and ipsapirone have a central hypotensive action that differs from that of clonidine in anaesthetised cats. Eur J Pharmacol138: 179–191.PubMedCrossRefGoogle Scholar
  23. 23.
    Martin KF, Mason R (1987): Isapirone is a partial agonist at 5-hydroxytryptamine1A(5- HT1A) receptors in the rat hippocampus: electrophysiological evidence. Eur J Pharmacol141: 479–483.PubMedCrossRefGoogle Scholar
  24. 24.
    Colino A, Halliwell JV (1986): 8-OH-DPAT is a strong antagonist of 5-HT actions in rat hippocampus. Eur J Pharmacol 130:151–152.PubMedCrossRefGoogle Scholar
  25. 25.
    Fozard JR, Kilbinger H (1985): 8-OH-DPAT inhibits transmitter release from guinea-pig enteric cholinergic neurones by activating 5-HT1A receptors. Br J Pharmacol 86:601P.CrossRefGoogle Scholar
  26. 26.
    Markstein R, Hoyer D, Engel G (1986): 5-HT1A receptors mediate stimulation of adenylate cyclase in rat hippocampus. Naunyn-Schmiedebergs Arch Pharmacol 333: 335–341.PubMedCrossRefGoogle Scholar
  27. 27.
    Schoeffter P, Hoyer D (1988): Centrally acting hypotensive agents with affinity for 5-HT1A binding sites inhibit forskolin-stimulated adenylate cyclase activity in calf hippocampus. Br J Pharmacol95: 975–985.PubMedCrossRefGoogle Scholar
  28. 28.
    De Vivo M, Maayani S (1986): Characterisation of the 5-hydroxytryptamine1A receptor- mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea-pig and rat hippocampus membranes. J Pharmacol Exp Ther238: 248–253.PubMedGoogle Scholar
  29. 29.
    Gilbert F, Brazell C, Tricklebank MD, Stahl S (1988): Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentration. Eur J Pharmacol147: 431–439.PubMedCrossRefGoogle Scholar
  30. 30.
    Chauloff F, Jeanrenaud B (1987): 5-HT1A and alpha-2 adrenergic receptors mediate the hyperglycemic and hypoinsulinemic effects of 8-Hydroxy-2-(di-n-propylamino) tetralin in the conscious rat. J Pharmacol Exp Ther 243: 1159–1166.Google Scholar
  31. 31.
    Bockaert J, Dumuis A, Bouhelal R, Sebben M, Cory RN (1987): Piperazine derivatives including the putative anxiolytic drugs buspirone and ipsapirone, are agonists at 5-HT1A receptors negatively coupled with adenylate cyclase in hippocampal neurones. Naunyn-Schmiedebergs Arch Pharmacol335: 588–592.PubMedCrossRefGoogle Scholar
  32. 32.
    Goldberg HL, Finnesty RJ (1979): The comparitive efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry136: 1184–1187.PubMedGoogle Scholar
  33. 33.
    Wouters W, Tulp MThM, Bevan P (1988): Flesinoxan lowers blood pressure and heart rate in cats via 5-HT1A receptors. Eur J Pharmacol149: 213–223.PubMedCrossRefGoogle Scholar
  34. 34.
    Yocca FD, Hyslop DK, Smith DW, Maayani S (1987): BMY 7378, a buspirone analog with high affinity, selectivity and low intrinsic activity at the 5-HT1A receptor in rat and guinea-pig hippocampal membranes. Eur J Pharmacol137: 293–294.PubMedCrossRefGoogle Scholar
  35. 35.
    Fozard JR, Hilbert M, Kidd EJ, Middlemiss DN, Mir AK, Tricklebank MD (1987): MDL 72832: a potent, selective and stereospecific ligand for 5-HT1A receptors. Br J Pharmacol90: 273 P.CrossRefGoogle Scholar
  36. 36.
    Wouters W, Rademaker B (1988): Discrepancies between 5-HT1A binding sites in the rat CNS and the guinea-pig ileum. Proc Cardiovascular Pharmacology of 5-HT Symposium. Amsterdam P62.Google Scholar
  37. 37.
    Engel G, Göthert M, Hoyer D, Schliker E, Hillenbrand K (1986): Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Naunyn Schmiedebergs Arch Pharmacol332: 1–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Holt SE, Cooper M, Wyllie JH (1986): On the nature of the receptor mediating the action of 5-hydroxytryptamine in potentiating responses of the mouse urinary bladder to electrical stimulation. Naunyn Schmiedebergs Arch Pharmacol334: 333–340.PubMedCrossRefGoogle Scholar
  39. 39.
    Moldering GJ, Fink K, Schliker E, Gothert M (1987): Inhibition of noradrenaline release via presynaptic 5-HT1B receptors of the rat vena cava. Naunyn Schmiedebergs Arch Pharmacol336: 245–250.Google Scholar
  40. 40.
    Bouhelal R, Smounya L, Bockaert J (1988): 5-HT1B receptors are negatively coupled with adenylate cyclase in rat substantia nigra. Eur J Pharmacol 151:189–196.PubMedCrossRefGoogle Scholar
  41. 41.
    Hoyer D, Pazos A, Probst A, Palacios JM (1986): Serotonin receptors in human brain. 1. Characterisation and autoradiographic localisation of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Res376: 85–96.PubMedCrossRefGoogle Scholar
  42. 42.
    Hoyer D (1988): Molecular pharmacology and biology of 5-HTlc receptors. Trends in Pharmacol Sci9: 89–94.CrossRefGoogle Scholar
  43. 43.
    Feniuk W, Humphrey PPA, Perren MJ, Watts AD (1985): A comparison of 5-hydroxytryptamine receptors mediating contraction in rabbit aorta and dog saphenous vein: evidence for different receptor types obtained by use of selective agonists and antagonists. Br J Pharmacol86: 697–704.PubMedCrossRefGoogle Scholar
  44. 44.
    Saxena PR, Lawang A (1985): A comparison of cardiovascular and smooth muscle effects of 5-hydroxytryptamine and 5-carboxamidotryptamine, a compound with selectivity for 5-HT1, binding sites. Arch Int Pharmacodyn 211: 235–252.Google Scholar
  45. 45.
    Saxena PR, Mylecharane EJ, Heiligers J (1985): Analysis of the heart rate effects of 5-hydroxytryptamine in the cat; Mediation of tachycardia by 5-HT1,-like receptors. Naunyn Schmiedebergs Arch Pharmacol330: 121–129.PubMedCrossRefGoogle Scholar
  46. 46.
    Saxena PR, Verdouw PD (1985): 5-Carboxamide tryptamine, a compound with high affinity for 5-HT1, binding sites, dilates arterioles and constricts arteriovenous anastomoses. Br J Pharmacol 84: 533–544.PubMedCrossRefGoogle Scholar
  47. 47.
    Schoeffter P, Waeber C, Palacios JM, Hoyer D (1988): The 5-hydroxytryptamine 5-HT1D receptor subtype is negatively coupled to adenylate cyclase in calf susbtantia nigra. Naunyn-Schmiederbergs Arch. Pharmacol337: 602–607.Google Scholar
  48. 48.
    Connor HE, Feniuk W, Humphrey PPA, Perren MJ (1986): 5-carboxamidotryptamine is a selective agonist at 5-hydroxytryptamine receptors mediating vasodilatation and tachycardia in anaesthetised cats. Br J Pharmacol 87:417–426.PubMedCrossRefGoogle Scholar
  49. 49.
    Connor HE, Feniuk W, Humphrey PPA (1989): Characterisation of 5-HT receptors mediating contraction of canine and primate basilar artery using GR43175, a selective 5-HT,-like receptor agonist. Br J Pharmacol96: 379–387.PubMedCrossRefGoogle Scholar
  50. 50.
    Parson AA, Whalley ET, Feniuk W, Connor HE, Humphrey PPA (1989): 5-HT1-like receptors mediate 5-hydroxytryptamine induced contraction of human isolated basilar artery. Br J Pharmacol 96:434–449.CrossRefGoogle Scholar
  51. 51.
    Feniuk W, Humphrey PPA, Watts AD (1981): Further characterisation of pre- and postjunctional receptors for 5-hydroxytryptamine in isolated vasculature. Br J Pharmacol73: 191–192 P.Google Scholar
  52. 52.
    Feniuk W, Humphrey PPA, Watts AD (1984): 5-Carboxamidotryptamine—a potent agonist at 5-hydroxytryptamine receptors mediating relaxation. Br J Pharmac 82:209P.Google Scholar
  53. 53.
    Trevethick MA, Feniuk W, Humphrey PPA (1986): 5-Carboxamidotryptamine: A potent agonist mediating relaxation and elevation of cyclic AMP in the isolated neonatal porcine vena cava. Life Sci 38:1521–1528.PubMedCrossRefGoogle Scholar
  54. 54.
    Sumner MJ, Humphrey PPA, Feniuk W (1987): Characterisation of the 5-HT1 like receptor mediating relaxation of porcine vena cava. Br J Pharmacol 92: 574 P.Google Scholar
  55. 55.
    Sumner MJ, Feniuk W, Humphrey PPA (1989): Further characterisation of the 5-HT receptor mediating vascular relaxation and elevation of cyclic AMP in isolated porcine vena cava. BrJPharmac (In press).Google Scholar
  56. 56.
    Feniuk W, Humphrey PPA, Perren MJ (1989): The selective carotid arterial vasoconstrictor action of GR43175 in anaesthetised dogs. Br J Pharmacol96: 83–90.PubMedCrossRefGoogle Scholar
  57. 57.
    Middlemiss DN, Bremer ME, Smith SM (1988): A pharmacological analysis of the 5-HT receptors mediating inhibition of 5-HT release in the guinea-pig frontal cortex. Eur J Pharmacol157: 101–108.PubMedCrossRefGoogle Scholar
  58. 58.
    Peroutka SJ, McCarthy BG (1989): Sumatriptan (GR43175) interacts selectively with 5-HT1B and 5-HT1D binding sites. Eur J Pharmacol163: 133–136.PubMedCrossRefGoogle Scholar
  59. 59.
    Sumner MJ, Humphrey PPA (1989): 5-HT1D binding sites in porcine brain can be subdivided by GR43175. Br J Pharmacol 98:29–31.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1990

Authors and Affiliations

  • Wasyl Feniuk
  • Patrick P. A. Humphrey

There are no affiliations available

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