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Preclinical Development of a Radioligand for the Study of Central 5-HT1A Receptors with PET — [11C]Way-100635

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PET for Drug Development and Evaluation

Part of the book series: Developments in Nuclear Medicine ((DNUM,volume 26))

Abstract

N-(2-(1-(4-(2-Methoxyphenyl)-1 -piperazinyl)ethyl))-N-(2-pyridyl)cyclohexanecarboxamide (WAY-100635) has properties that favour its development as the first radioligand for studies of 5-HT1A receptors in vivo with positron emission tomography (PET). These include high potency, high selectivity, pure antagonist action and amenability to labelling with the positron-emitter, carbon-11 (t 1/2 = 20.4 min). Here the status of our preclinical development of [11 C] WAY-100635 as a PET radioligand is summarised. On the basis of studies in rats and human volunteers, it is concluded that [11C]WAY-100635 is a promising radioligand for the study of central 5-HT 1A receptors with potential for application to the study of neuropsychiatric disorders and to the human pharmacology of psychoactive drugs.

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References

  1. Pike VW. Positron-emitting radioligands for studies in vivo — probes for human psychopharmacology.J Psychopharmacology 1993; 7: 139–158.

    Article  CAS  Google Scholar 

  2. Mazière B, Coenen HH, Halldin C, Nâgren K, Pike VW. PET radioligands for dopamine receptors and re-uptake sites: chemistry and biochemistry. Nucl Med Biol 1992; 19: 497–512.

    Google Scholar 

  3. Crouzel C, Guillaume M, Barré L, Lemaire C, Pike VW. Ligands and tracers for PET studies of the 5HT system —current status. Nucl Med Biol 1992; 19: 857–870.

    CAS  Google Scholar 

  4. Humphrey PPA, Hartig P, Hoyer D. A proposed new nomenclature for 5-HT receptors. Trends Pharm Sci 1993; 14: 233–236.

    Article  PubMed  CAS  Google Scholar 

  5. Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat J-L, Muscatelli F, Mattei, M-G, Hen R. Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors; cloning, functional expression, and chromosomal localization. Mol Pharmacol 1993; 43: 313–319.

    PubMed  CAS  Google Scholar 

  6. Monsma FJ, Shen Y, Ward RP, Hamblin MW, Sibley DR. Cloning and expression of a novel serotonin receptor with high affinity for psychotropic drugs. Mol Pharmacol 1993; 43: 320–327.

    PubMed  CAS  Google Scholar 

  7. Lovenberg TW, Baron BM, de Lecea L, Miller JD, Prosser RA, Rea MA, Foye PE, Racke M, Slone AL, Siegel BW, Danielson PE, Sutcliffe JG, Erlander MG. A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron 1993; 11: 449–458.

    Article  PubMed  CAS  Google Scholar 

  8. Dourish CT. Brain 5-HT1A receptors and anxiety. In: Dourish CT, Ahlenius S, Hutson PH, editors. Brain 5-HT1A receptors; Chichester: Ellis Horwood Ltd., 1987: pp 261.

    Google Scholar 

  9. Pedigo NW, Yamamura HI, Nelson DL. Discrimination of multiple [3H]5-hydroxytryptamine binding sites by the neuroleptic perone in rat brain. J Neurochem 1981; 36: 220–226.

    Article  PubMed  CAS  Google Scholar 

  10. Middlemiss DN, Fozard JR. 8-Hydroxy-2-(di-n-propylamino)tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol 1983; 90: 151–153.

    Article  PubMed  CAS  Google Scholar 

  11. Gozlan H, El Mestikawy S, Pichat L, Glowinski J, Hamon M. Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT. Nature 1983; 305: 140–142.

    Article  PubMed  CAS  Google Scholar 

  12. Palacios JM, Pazos A, Hoyer D. Characterisation and mapping of 5-HT1A sites in the brains of animals and man. In: Dourish CT, Ahlenius S, Hutson PH, editors. Brain 5-HTiA receptors. Ellis Horwood Ltd., Chichester: 1987: pp 67-81.

    Google Scholar 

  13. Verge D, Daval G, Patey A, Gozlan H, El Mestikawy S, Hamon M. Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. Eur J Pharmacol. 1985; 113: 463-464.

    Article  PubMed  CAS  Google Scholar 

  14. Lesch KP, Osterheider M. In: Briley M, File SE, editors. New concepts in anxiety. Macmillan Press Ltd., 1991: pp 130-144.

    Google Scholar 

  15. Fletcher A, Cliffe IA, Dourish CT. Silent 5-HTiA receptor antagonists; utility as research tools and therapeutic agents. Trends Pharm Sci, 1993; 14: 441-448.

    Article  CAS  Google Scholar 

  16. Francis PT, Pangalos MN, Pearson RCA, Middlemisss DN, Stratmann GC, Bowen DM. 5-Hydroxytryptamine1A but not 5-hydroxytryptamine2 receptors are enriched on neocortical pyramidal neurones destroyed by intrastriatal volkensin. J Pharmacol & Exp Therapeutics 1992; 18: 631-642.

    Google Scholar 

  17. Halldin C, Wikstrom H, Swahn C-G, Sedvall G, Stjernlof P, Farde L. Preparation of [propyl-nC]OSU 191, a highly potent and selective 5-HTiA agonist for PET. J Label Compd Radiopharm 1994; 35: 494-495.

    Google Scholar 

  18. Thorell J-O, Stone-Elander S, Ingvar M. Microwave-induced synthesis of [N-propyl-1iC]-8-hydroxy-2-(di-n-propylamino)tetralin. J Label Compd Radiopharm 1994; 35: 496.

    Google Scholar 

  19. Pike VW, Hume SP, Ashworth S, Opacka-Juffry J, McCarron JA, Cliffe IA, Fletcher I, White AC. Evaluation of radiolabelled WAY-100635 as a potential ligand for in vivo studies of central 5HTiA receptors, Presented at the IUPHAR satellite meeting on serotonin, Chicago, August 1994. Behaviourial Brain Research. Elsevier. Editor Huston JP. In press.

    Google Scholar 

  20. Hume SP, Ashworth S, Opacka-Juffry J, Ahier RG, Lammertsma AA, Pike VW, Cliffe IA, Fletcher A, White AC. Evaluation of [0-methyl- 3 H]WAY-100635 as an in vivo radioligand for 5-HTiA receptors in rat brain. Eur J Pharmacol 1994; 271: 515-523.

    Article  PubMed  CAS  Google Scholar 

  21. Laporte A-M, Lima L, Gozlan H, Hamon M. Selective labelling of brain 5-HT1A receptors by [3H]WAY 100635 in the mouse. Eur J Pharmacol 1994; 271: 505-514.

    Article  PubMed  CAS  Google Scholar 

  22. Mathis CA, Simpson NR, Mahmood K, Kinahan PE, Mintun MA. [“C]WAY 100635: A radioligand for imaging 5-HTiA receptors with positron emission tomography. Life Sci 1994; 55: 403-407.

    Article  Google Scholar 

  23. Pike VW, McCarron JA, Hume SP, Ashworth S, Opacka-Juffry J, Osman S, Lammertsma AA, Poole KG, Fletcher A, White AC, Cliffe IA. Pre-clinical development of a radioligand for studies of central 5-HT1A receptors in vivo — [HCJWAY-100635. Med Chem Res. In press.

    Google Scholar 

  24. Shiue C-Y, Shiue GC, Zhuang ZP, Kung M-P, Kung HF. Synthesis of no-carrier-added 4(2′-methoxy-phenyl)-l-[2,(N-2″-pyridinyl)-/?-[F-18]fluoro-benzamido]ethylpiperazine (2b) as a potential 5-HTiA receptor ligand for PET studies. J Nucl Med 1994; 35: 252P.

    Google Scholar 

  25. Zhuang Z-P, Kung MP, Kung HF. Synthesis and evaluation of 4-(2,-methoxyphenyl-l-[2,-[-2,,-pyridinyl)-/7-iodobenzamido)ethyl]piperazine (p-MPPI): a new iodinated 5-HTiA ligand. J Med Chem 1994; 37: 1406-1407.

    Article  PubMed  CAS  Google Scholar 

  26. Kung HF, Zhuang Z-P, Kung M-P, Mozley PD, Kim H-J, McElgin W, Frederick D. [I-123]P-MPPI: A potential 5-HT1A receptor antagonist for SPECT imaging. J Nucl Med 1994; 35: 93P.107

    Google Scholar 

  27. Kung HF, Kung M-P, Clarke W, Maayani S, Zhuang Z-P. A potential 5-HT1A receptor antagonist: p-MPPl Life Sci 1994: 55; 1459-1462.

    Article  PubMed  CAS  Google Scholar 

  28. Cliffe I A, The design of selective 5-HT1A receptor antagonists, 206th National Meeting of the American Chemical Society, August 22-27, 1993, Chicago, II, Abstr. MEDI 30, 1993.

    Google Scholar 

  29. Fletcher A, Bill DJ, Cliffe IA, Forster EA, Reilly Y. A pharmacological profile of WAY-100635, a potent and highly selective 5-HT1A receptor antagonist. Br J Pharmacol 1994; 112: 91P.

    Google Scholar 

  30. Khawaja X, Ifill A, Ennis C. Characterisation of the binding of a novel and selective antagonist radioligand, PH]WAY-100635, to the 5-HTiA receptor in rat brain. Presented at the IUPHAR satellite meeting on serotonin, Chicago, August 1994. Behaviourial Brain Research. Elsevier. Editor, Huston JP. In press.

    Google Scholar 

  31. Gurling J, Ashworth-Preece MA, Dourish CT, Routledge C. Effects of acute and chronic treatment with the selective 5-HTiA receptor antagonist WAY-100635 on hippocampal 5-HT release in vivo Br J Pharmacol 1994; 112: 299P.

    Article  Google Scholar 

  32. Hartley JE, Forster EA, Fletcher A. The effects of WAY-100635, a potent and selective 5-HTiA receptor antagonist, on feeding and 8-OH-DPAT-induced feeding in the rat. Br J Pharmacol 1994; 112: 298P.

    Google Scholar 

  33. Critchley DJP, Wilson KMR, Middlefell VC, Dourish CT. Plasma glucose and cardiovascular studies in the rat with WAY-100635, a selective, potent 5-HTiA receptor antagonist. Br J Pharmacol 1994; 112: 109P.

    Google Scholar 

  34. Lammertsma A.A., Bench CJ, Hume SP, Osman S, Gunn K, Brooks DJ, Frackowiak RSJ. Comparison of methods for analysis of clinical [nC]raclopride studies. J. Cerebr Blood Flow Metab. In press.

    Google Scholar 

  35. Radja F, Duval G, Hamon M, Verge D. Pharmacological and physicochemical properties of pre- versus postsynaptic 5-hydroxytryptamineiA receptor binding sites in the rat brain: a quantitative autoradiographic study. J Neurochem 1992; 58: 1338.

    Article  PubMed  CAS  Google Scholar 

  36. Kawai N, Yamamoto T, Baba A, Yamamoto H, Moroji T. Inhibitory effect of idazoxan on forskolin-stimulated adenylate cyclase activity through 5-hydroxytryptamine1A receptors. Arzneim-Fosch Drug Res 1994; 44: 1-3.

    CAS  Google Scholar 

  37. Cliffe IA, Brightwell CI, Fletcher A, Forster EA, Mansell HL, Routledge C, White AC. (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-l-yl)-2-phenylpropanamide (S)-WAY-100135: a selective antagonist at presynaptic and postsynaptic 5-HTiA receptors. J Med Chem 1993; 36: 1509-1510.

    Article  PubMed  CAS  Google Scholar 

  38. Fletcher A, Bill DJ, Bill SJ, Cliffe IA, Dover GM, Forster EA, Glen DCB, Haskins JT, Jones D, Mansell HL, Reilly Y. WAY-100135: a novel selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. Eur J Pharmacol 1993; 237: 283-291.

    Article  PubMed  CAS  Google Scholar 

  39. Bloomfield PM, Rajeswaren S, nks TJ, Hume SP, Myers R, Ashworth S, Jones WF, Clifford KM, Byars LG, Young J, Andreaco M, Williams CW, Lammertsma AA, Jones T. Design and physical characteristics of a small animal positron emission tomograph. Phys Med Biol; in press.

    Google Scholar 

  40. Luthra SK, Turton DR, Price G, Ahier R, Martin F, Hume S, Cremer J. The determination of unchanged [nC]diprenorphine, [nC]L-deprenyl and [HCJraclopride in plasma by HPLC. J Label Compd Radiopharm 1991; 30: 378-379.

    Google Scholar 

  41. Luthra SK, Osman S, Turton DR, Vaja V, Dowsett K, Brady F. An automated system 108based on solid phase extraction and HPLC for the routine determination in plasma of unchanged [nC]-L-deprenyl; [nC]diprenorphine; [HC]flumazenil; [nC]raclopride and [HC]Scherring 23390. J Label Compd Radiopharm 1993; 32: 518-520.

    Google Scholar 

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Authors
  1. Victor W. Pike
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  2. Ian A. Cliffe
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  3. Allan Fletcher
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  4. Susan P. Hume
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  5. Julie A. McCarron
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  6. Sharon Ashworth
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  7. Jolanta Opacka-Juffry
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  8. Safiye Osman
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  9. Adriaan A. Lammertsma
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  10. Keith G. Poole
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  11. Alan C. White
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  12. Christopher J. Bench
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  13. Paul Grasby
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Editor information

Editors and Affiliations

  1. Hôpital Neuro-cardiologique, Lyon, France

    D. Comar

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© 1995 Springer Science+Business Media Dordrecht

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Pike, V.W. et al. (1995). Preclinical Development of a Radioligand for the Study of Central 5-HT1A Receptors with PET — [11C]Way-100635. In: Comar, D. (eds) PET for Drug Development and Evaluation. Developments in Nuclear Medicine, vol 26. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-0429-6_9

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  • DOI: https://doi.org/10.1007/978-94-011-0429-6_9

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-4191-1

  • Online ISBN: 978-94-011-0429-6

  • eBook Packages: Springer Book Archive

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