European Neuropsychopharmacology
Volume 22, Issue 2 , Pages 92-99 , February 2012

Concomitant blockade of 5-HT1A receptor and 5-HT transporter: Use of the Hunter Serotonin Toxicity Criteria in a clinical pharmacology study

  • V. Parks

      Affiliations

    • Early Development and Clinical Pharmacology, Wyeth Research, Paris, France
    • Corresponding Author InformationCorresponding author at: Early Development & Clinical Pharmacology, Pfizer Global Research and Development, Coeur Défense — Tour A — La Défense 4, 92931 Paris La Defense Cedex, France. Tel.: +33 6 14 45 56 03; fax: +33 1 4102 7441.
    • Now at Pfizer Global Research and Development, Paris, France.
    • ,
  • A.W. Philipp

      Affiliations

    • VasoTissue Technologies, Berlin, Germany
    • Formerly at Icon Development Solutions, Manchester, United Kingdom.
    • ,
  • S. Raje

      Affiliations

    • Pfizer Inc., Collegeville, PA, USA
    • ,
  • A. Plotka

      Affiliations

    • Pfizer Inc., Collegeville, PA, USA
    • ,
  • L.E. Schechter

      Affiliations

    • Pfizer Inc., Groton, CT, USA
    • ,
  • J. Connell

      Affiliations

    • Icon Development Solutions, Manchester, United Kingdom
    • ,
  • S. Chalon

      Affiliations

    • Early Development and Clinical Pharmacology, Wyeth Research, Paris, France
    • Now at Pfizer Global Research and Development, Paris, France.

Received 2 April 2011 ,Revised 24 May 2011 ,Accepted 10 June 2011.

References 

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  3. Childers WE, Harrison BL, Abou-Gharbia MA, Raje S, Parks V, Pangalos MN, et al. Lecozotan hydrochloride. Drugs Future. 2007;32(5):399–407
  4. Dingemans J, Wallnöfer A, Gieschke R, Guentert T, Amrein R. Pharmacokinetic and pharmacodynamic interactions between fluoxetine and moclobemide in the investigation of the development of the “serotonin syndrome”. Clin. Pharmacol. Ther. 1998;63:403–413
  5. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96:635–642
  6. Gillman PK. The serotonin syndrome and its treatment. J. Psychopharmacol. 1999;13(1):100–109
  7. Gutierrez M, Abramowitz W. Steady-state pharmacokinetics of citalopram in young and elderly subjects. Pharmacotherapy. 2000;20(12):1441–1447
  8. Herrlin K, Yasui-Furukori N, Tybring G. Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes. Br. J. Clin. Pharmacol. 2003;56:415–421
  9. Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J. Toxicol. Clin. Toxicol. 2004;42(3):277–285
  10. Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: a practical approach to diagnosis and treatment. MJA. 2007;187:361–365
  11. Leuchter AF, Lesser IM, Trivedi MH. An open pilot study of the combination of escitalopram and buproprion-SR for outpatients with major depressive disorder. J. Psychiatr. Pract. 2008;14(5):271–280
  12. Lowe SL, Yeo KP, Teng L, Soon D, Pan A, Wise A, et al. L-5-Hydroxytryptophan augments the neuroendocrine response to a SSRI. Psychoneuroendocrinology. 2006;31:473–484
  13. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine. 2000;79:201–209
  14. Patat A, Parks V, Raje S, Plotka , Chassard D, Le Coz F. Safety, tolerability, pharmacokinetics and pharmacodynamics of ascending single and multiple doses of lecozotan in healthy young and elderly subjects. Br. J. Clin. Pharmacol. 2009;67(3):299–308
  15. Plotka A, Parks V, Raje S, Patat A, Paul J, El Gaaloul M, et al. Single-dose, double-blind, crossover, placebo-and moxifloxacin controlled study of the effects of lecozotan SR, a novel 5HT1A antagonist, on cardiac repolarization in healthy adult subjects. Poster presented at the American College of Clinical Pharmacology (ACCP). September, 2008;
  16. Raje S, Patat A, Parks V, Schechter LE, Plotka A, Paul J, et al. A positron emission tomography study to assess binding of lecozotan, a novel 5-hydroxytryptamine-1A silent antagonist, to brain 5-HT1A receptors in healthy young and elderly subjects, and in patients with Alzheimer's disease. Clin. Pharm. Ther. 2008;83(1):86–96
  17. Schechter LE, et al. Lecozotan (SRA-333): a selective serotonin 1A receptor antagonist that enhances the stimulated release of glutamate and acetylcholine in the hippocampus and possesses cognitive-enhancing properties. J. Pharmacol. Exp. Ther. 2005;314:1274–1289
  18. Segrave R, Nathan PJ. Pindolol augmentation of selective serotonin reuptake inhibitors: accounting for the variability of results of placebo-controlled double-blind studies in patients with major depression. Hum. Psychopharmacol. 2005;20:163–174
  19. Segrave R, Croft RJ, Illic S, Luan Phan K, Nathan PJ. Pindolol does not augment central serotonin function increases to citalopram in humans: an auditory evoked potential investigation. Pharmacol. Biochem. Behav. 2006;85:82–90
  20. Yu BN, Chen GL, He N, et al. Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19. Drug Metab. Dispos. 2003;31(10):1255–1259

PII: S0924-977X(11)00131-3

doi: 10.1016/j.euroneuro.2011.06.002

European Neuropsychopharmacology
Volume 22, Issue 2 , Pages 92-99 , February 2012

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