European Neuropsychopharmacology
Volume 20, Issue 8 , Pages 582-593 , August 2010

An in vivo pharmacological evaluation of pardoprunox (SLV308) — A novel combined dopamine D2/D3 receptor partial agonist and 5-HT1A receptor agonist with efficacy in experimental models of Parkinson's disease

  • C.A. Jones

      Affiliations

    • Abbott Pharmaceuticals B.V., Weesp, The Netherlands (formerly Solvay Pharmaceuticals B.V.)
    • These authors contributed equally.
    • Present address: School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, NG7 2UH, UK.
    • ,
  • L.C. Johnston

      Affiliations

    • Neurodegenerative Diseases Research Centre, School of Biomedical and Health Sciences, King's College London, London SE1 1UL, UK
    • These authors contributed equally.
    • Present address: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK.
    • ,
  • M.J. Jackson

      Affiliations

    • Neurodegenerative Diseases Research Centre, School of Biomedical and Health Sciences, King's College London, London SE1 1UL, UK
    • ,
  • L.A. Smith

      Affiliations

    • Neurodegenerative Diseases Research Centre, School of Biomedical and Health Sciences, King's College London, London SE1 1UL, UK
    • ,
  • G. van Scharrenburg

      Affiliations

    • Abbott Pharmaceuticals B.V., Weesp, The Netherlands (formerly Solvay Pharmaceuticals B.V.)
    • ,
  • S. Rose

      Affiliations

    • Neurodegenerative Diseases Research Centre, School of Biomedical and Health Sciences, King's College London, London SE1 1UL, UK
    • ,
  • P.G. Jenner

      Affiliations

    • Neurodegenerative Diseases Research Centre, School of Biomedical and Health Sciences, King's College London, London SE1 1UL, UK
    • ,
  • A.C. McCreary

      Affiliations

    • Abbott Pharmaceuticals B.V., Weesp, The Netherlands (formerly Solvay Pharmaceuticals B.V.)
    • Corresponding Author InformationCorresponding author. Tel.: +31 294 479 514; fax: +31 294 410 069.

Received 28 September 2009 ,Revised 5 February 2010 ,Accepted 10 March 2010.

References 

  1. Akai T, Yamaguchi M, Mizuta E, Kuno S. Effects of terguride, a partial D2 agonist, on MPTP-lesioned parkinsonian cynomolgus monkeys. Ann. Neurol. 1993;33:507–511
  2. Arnt J, Hyttel J. Dopamine D2 agonists with high and low efficacies: differentiation by behavioural techniques. J. Neural. Transm. Gen. Sect. 1990;80:33–50
  3. Bardin L, Kleven MS, Barret-Grevoz C, Depoortere R, Newman-Tancredi A. Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties. Neuropsychopharmacology. 2006;31:1869–1879
  4. Baronti F, Mouradian MM, Conant KE, Giuffra M, Brughitta G, Chase TN. Partial dopamine agonist therapy of levodopa-induced dyskinesias. Neurology. 1992;42:1241–1243
  5. Bibbiani F, Oh JD, Chase TN. Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Neurology. 2001;57:1829–1834
  6. Bravi D, Davis T, Mouradian M, Chase TN. Treatment of Parkinson's with the dopamine partial agonist EMD 49980. Mov. Disord. 1993;8:195–197
  7. Bronzova, J., Sampaio, C., Hauser, R.A., Lang, A.E., Rascol, O., Theeuwes, A., Serge, V., van de Witte, S.V., van Scharrenburg, G., in press. Double-blind study of pardoprunox, a new partial dopamine agonist, in early Parkinson's disease. Mov. Disord.
  8. Brücke T, Danielczyk W, Simányi M, Sofic E, Riederer P. Terguride: partial dopamine agonist in the treatment of Parkinson's disease. Adv. Neurol. 1987;45:573–576
  9. Carlsson A. Treatment of Parkinson's with l-DOPA: the early discovery phase, and a comment on current problems. J. Neural. Transm. 2002;109:777–787
  10. Clark D, Furmidge LJ, Petry N, Tong ZY, Ericsson M, Johnson D. Behavioural profile of partial D2 dopamine receptor agonists. 1. Atypical inhibition of d-amphetamine-induced locomotor hyperactivity and stereotypy. Psychopharmacology (Berl). 1991;105:381–392
  11. Corsini G, Bonuccelli U, Rainer E, Del Zompo M. Therapeutic efficacy of a partial dopamine agonist in drug-free parkinsonian patients. J. Neural. Transm. 1985;64:105–111
  12. Costall B, Naylor RJ. A comparison of circling models for the detection of antiparkinson activity. Psychopharmacologia. 1975;41:57–64
  13. Costall B, Naylor RJ, Pycock C. Non-specific supersensitivity of striatal dopamine receptors after 6-hydroxydopamine lesion of the nigrostriatal pathway. Eur. J. Pharmacol. 1976;35:276–283
  14. Critchley P, Parkes D. Transdihydrolisuride in Parkinsonism. Clin. Neuropharmacol. 1987;10:57–64
  15. Doder M, Rabiner EA, Turjanski N, Lees AJ, Brooks DJ. Tremor in Parkinson's disease and serotonergic dysfunction: an 11C-WAY 100635 PET study. Neurology. 2003;60:601–605
  16. Fenton HM, Leszczak E, Gerhardt S, Liebman JM. Evidence for heterogeneous rotational responsiveness to apomorphine, 3-PPP and SKF 38393 in 6-hydroxydopamine-denervated rats. Eur. J. Pharmacol. 1984;106:363–372
  17. Fox SH, Chuang R, Brotchie JM. Serotonin and Parkinson's disease: on movement, mood and madness. Mov. Disord. 2009;24:1255–1266
  18. Gerber R, Altar CA, Liebman JM. Rotational behavior induced by 8-hydroxy-DPAT, a putative 5HT-1A agonist, in 6-hydroxydopamine-lesioned rats. Psychopharmacology (Berl). 1988;94:178–182
  19. Giovannini P, Piccolo I, Genitrini S, Girotti F, Testa D, Scigliano G, et al. Terguride in the treatment of Parkinson's disease: preliminary experience. Ital. J. Neurol. Sci. 1990;11:381–385
  20. Glennon JC, van Scharrenburg G, Ronken E, Hesselink MB, Reinders JH, van Der Neut M, et al. In vitro characterization of SLV308 (7-[4-methyl-1-piperazinyl]-2(3H)-benzoxazolone, monohydrochloride): a novel partial dopamine D2 and D3 receptor agonist and serotonin 5-HT1A receptor agonist. Synapse. 2006;60:599–608
  21. Hagan JJ, Middlemiss DN, Sharpe PC, Poste GH. Parkinson's disease: prospects for improved drug therapy. Trends Pharmacol. Sci. 1997;18:156–163
  22. Heinrich JN, Brennan J, Lai MH, Sullivan K, Hornby G, Popiolek M, et al. Aplindore (DAB-452), a high affinity selective dopamine D2 receptor partial agonist. Eur. J. Pharmacol. 2006;552:36–45
  23. Hornykiewicz O. Brain monoamines and parkinsonism. Natl. Inst. Drug Abuse Res. Monogr. Ser. 1975;3:13–21
  24. Ikoma Y, Akai T, Nakata Y, Hara K, Wachtel H, Yamaguchi M. Effects of terguride, an ergot alkaloid derivative, on the central nervous system: biochemical and behavioral studies. Nippon Yakurigaku Zasshi. 1993;102:113–129
  25. Iravani MM, Tayarani-Binazir K, Chu WB, Jackson MJ, Jenner P. In MPTP-treated primates, the selective 5-HT 1A receptor agonist (R)-(+)-8-OHDPAT inhibits l-DOPA induced dyskinesia but only with increased motor disability. J. Pharmacol. Exp. Ther. 2006;319:1225–1234
  26. Jackson MJ, Al-Barghouthy G, Pearce RKB, Smith L, Hagan JJ, Jenner P. Effect of 5-HT1B/D receptor agonist and antagonist administration on motor function in MPTP-treated common marmosets. Pharmacol. Biochem. Behav. 2007;79:391–400
  27. Jenner P. Pharmacology of dopamine agonists in the treatment of Parkinson's disease. Neurology. 2002;58(S1):S1–S8
  28. Jenner P. Avoidance of dyskinesia: preclinical evidence for continuous dopaminergic stimulation. Neurologia. 2004;62(S1):S47–S55
  29. Jenner P. Preventing and controlling dyskinesia in Parkinson's disease — a view of current knowledge and future opportunities. Mov. Disord. 2008;23(S3):S585–S598
  30. Jenner P, Sheehy M, Marsden CD. Noradrenaline and 5-hydroxytryptamine modulation of brain dopamine function: implications for the treatment of Parkinson's disease. Br. J. Clin. Pharmacol. 1983;15(S2):277S–289S
  31. Jones CA, McCreary AC. Serotonergic approaches in the development of novel antipsychotics. Neuropharmacology. 2008;55:1056–1065
  32. Kannari K, Yamato H, Shen H, Tomiyama M, Suda T, Matsunaga M. Activation of 5-HT(1A) but not 5-HT(1B) receptors attenuates an increase in extracellular dopamine derived from exogenously administered l-DOPA in the striatum with nigrostriatal denervation. J. Neurochem. 2001;76:1346–1353
  33. Kannari K, Kurahashi K, Tomiyama M, Maeda T, Arai A, Baba M, et al. Tandospirone citrate, a selective 5-HT1A agonist, alleviates l-DOPA-induced dyskinesia in patients with Parkinson's disease. No To Shinkei. 2002;54:133–137
  34. Koller WC, Herbster G. Terguride, a mixed dopamine agonist–antagonist, in animal models of Parkinson's disease. Neurology. 1987;37:723–727
  35. Krause W, Humpel M. Pharmacokinetics of the dopamine partial agonist, terguride, in the rat and rhesus monkey. Eur. J. Drug Metab. Pharmacokinet. 1988;13:185–194
  36. Krause W, Trager H, Kuhne G, Sauerbrev N, Graf KG, Dorow R. Pharmacokinetics and endocrine effects of terguride in healthy subjects. Eur. J Clin. Pharmacol. 1990;38:609–615
  37. Kuoppamäki M, Al-Barghouthy G, Jackson MJ, Smith LA, Quinn N, Jenner P. l-DOPA dose and the duration and severity of dyskinesia in primed MPTP-treated primates. J. Neural. Transm. 2007;114:1147–1153
  38. Lange KW, Loschmann PA, Wachtel H, Horowski R, Jahnig P, Jenner P, et al. Terguride stimulates locomotor activity at 2months but not 10months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets. Eur. J. Pharmacol. 1992;212:247–252
  39. Löschmann PA, Smith LA, Lange KW, Jahnig P, Jenner P, Marsden CD. Motor activity following the administration of selective D-1 and D-2 dopaminergic drugs to MPTP-treated common marmosets. Psychopharmacology (Berl). 1992;109:49–56
  40. Maratos EC, Jackson MJ, Pearce RK, Cannizzaro C, Jenner P. Both short- and long-acting D-1/D-2 dopamine agonists induce less dyskinesia than l-DOPA in the MPTP-lesioned common marmoset (Callithrix jacchus). Exp. Neurol. 2003;179:90–102
  41. McCreary AC, Glennon JC, Ashby CR, Meltzer HY, Li Z, Reinders JH, et al. SLV313 (1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-4-[5-(4-fluoro-phenyl)-pyridin-3-ylmethyl]-piperazine monohydrochloride): a novel dopamine D2 receptor antagonist and 5-HT1A receptor agonist potential antipsychotic drug. Neuropsychopharmacology. 2007;32:78–94
  42. Millan MJ, Rivet JM, Canton H, Le Marouille-Girardon S, Gobert A. Induction of hypothermia as a model of 5-hydroxytryptamine1A receptor-mediated activity in the rat: a pharmacological characterization of the actions of novel agonists and antagonists. J. Pharmacol. Exp. Ther. 1993;264:1364–1376
  43. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A. Differential actions of antiparkinson agents at multiple classes of monoaminergic receptors. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J. Pharmacol. Exp. Ther. 2002;303:791–804
  44. Newman-Tancredi A, Cussac D, Audinot V, Nicolas JP, De Ceuninck F, Boutin JA, et al. Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor. J. Pharmacol. Exp. Ther. 2002;303:805–814
  45. Newman-Tancredi A, Cussac D, Quentric Y, Touzard M, Verrièle L, Carpentier N, et al. Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes. J. Pharmacol. Exp. Ther. 2002;303:815–822
  46. Nomoto M, Jenner P, Marsden CD. Alterations in motor behaviour produced by the isomers of 3-PPP in the MPTP-treated marmoset. Eur. J. Pharmacol. 1986;121:123–128
  47. Olanow W, Schapira AH, Rascol O. Continuous dopamine-receptor stimulation in early Parkinson's disease. Trends Neurosci. 2000;23(S10):S117–S126
  48. Olanow CW, Damier P, Goetz CG, Mueller T, Nutt J, Rascol O, et al. Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study). Clin. Neuropharmacol. 2004;27:58–62
  49. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. New York: Academic Press; 1998;
  50. Pearce RK, Banerji T, Jenner P, Marsden CD. De novo administration of ropinirole and bromocriptine induces less dyskinesia than l-DOPA in the MPTP-treated marmoset. Mov. Disord. 1998;13:234–241
  51. Pérez-Otaño I, Herrero MT, Oset C, De Ceballos ML, Luquin MR, Obeso JA, et al. Extensive loss of brain dopamine and serotonin induced by chronic administration of MPTP in the marmoset. Brain Res. 1991;567:127–132
  52. Pirtosek Z, Merello M, Carlsson A, Stern G. Preclamol and Parkinsonian fluctuations. Clin. Neuropharmacol. 1993;16:550–554
  53. Pirtosek Z, Merello M, Carlsson A, Stern G. Preclamol. A “designer drug” in the treatment of advanced Parkinson's disease. Adv. Neurol. 1996;69:535–540
  54. Rollema H, Mastebroek D, Wikstrom H, Svensson K, Carlsson A, Sundell S. Enantiomers of 3-(3,4-dihydroxyphenyl)- and 3-(3-hydroxyphenyl)-N-n-propylpiperidine: central pre- and postsynaptic dopaminergic effects and pharmacokinetics. J. Med. Chem. 1986;29:1889–1895
  55. Ruggieri S, Stocchi F, Baronti F, Viselli F, Horowski R, Lucarelli C, et al. Antagonist effect of terguride in Parkinson's disease. Clin. Neuropharmacol. 1991;14:450–456
  56. Saigusa T, Tuinstra T, Koshikawa N, Cools AR. High and low responders to novelty: effects of a catecholamine synthesis inhibitor on novelty-induced changes in behaviour and release of accumbal dopamine. Neuroscience. 1999;88:1153–1163
  57. Schapira AH, Bezard E, Brotchie J, Calon F, Collingridge GL, Ferger B, et al. Novel pharmacological targets for the treatment of Parkinson's disease. Nat. Rev. Drug Discov. 2006;5:845–854
  58. Smith L, De Salvia M, Jenner P, Marsden CD. An appraisal of the antiparkinsonian activity of piribedil in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- treated common marmosets. Mov. Disord. 1996;11:125–135
  59. Smith LA, Jackson MJ, Johnston L, Kuoppamaki M, Rose S, Al-Barghouthy G, et al. Switching from levodopa to the long-acting dopamine D2/D3 agonist piribedil reduces the expression of dyskinesia while maintaining effective motor activity in MPTP-treated primates. Neuropharmacology. 2006;29:112–125
  60. Tamminga CA, Cascella NG, Lahti RA, Lindberg M, Carlsson A. Pharmacologic properties of (−)-3PPP (preclamol) in man. J. Neural. Transm. Gen. Section. 1992;88:165–175
  61. Tricklebank MD, Forler C, Fozard JR. The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. Eur. J. Pharmacol. 1984;106:271–282
  62. Ungerstedt U, Arbuthnott GW. Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigro-striatal system. Brain Res. 1970;24:485–493

PII: S0924-977X(10)00061-1

doi: 10.1016/j.euroneuro.2010.03.001

European Neuropsychopharmacology
Volume 20, Issue 8 , Pages 582-593 , August 2010

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