Skip to main content

Advertisement

SpringerLink
Log in

Effects of the atypical antipsychotics olanzapine and risperidone on plasma prolactin levels in male rats: a comparison with clinical data

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Hyperprolactinaemia is a common side effect of antipsychotic treatment and the clinical consequences associated with this, e.g. sexual dysfunction, can have a negative impact on patient compliance.

Objectives

The aim of this study was to investigate the effect of the atypical antipsychotics olanzapine and risperidone on prolactin levels in rats using different treatment regimes and to compare these data with those reported clinically. Methods: All experiments were carried out in male CD rats. In separate studies, the effects of acute, sub-chronic (7 days) and chronic (28 days) olanzapine and risperidone administration on prolactin levels were determined. Further studies investigated the time course of the prolactin response following olanzapine and risperidone treatment over 24 h.

Results

Both drugs significantly increased prolactin levels in a similar manner following acute administration, in keeping with clinically reported data. However, this elevation was still present following sub-chronic and chronic treatment, contrasting with clinical data with respect to olanzapine but not risperidone. Over 24 h, olanzapine demonstrated a more transient elevation of prolactin levels, whereas risperidone caused a robust and persistent increase in prolactin up to 24 h post-dose, closely mimicking clinical results.

Conclusions

The present study has demonstrated that olanzapine and risperidone display similar effects on prolactin levels in the rat following acute and chronic administration but differ in their prolactin response over a 24-h period. In conclusion, prolactin levels in rats following atypical antipsychotic treatment may not be fully predictive of the clinical situation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aravagiri M, Teper Y, Marder SR (1999) Pharmacokinetics and tissue distribution of olanzapine in rats. Biopharm Drug Dispos 20:369–377

    Article  PubMed  CAS  Google Scholar 

  • Aravagiri M, Marder SR (2002) Brain, plasma and tissue pharmacokinetics of risperidone and 9-hydroxyrisperidone after separate oral administration to rats Psychopharmacology 159:424–431

    Article  PubMed  CAS  Google Scholar 

  • Baptista T, Araujo de Baptista E, Ying Kin NM, Beaulieu S, Walker D, Joober R, Lalonde J, Richard D (2002) Comparative effects of the antipsychotics sulpiride or risperidone in rats I: bodyweight, food intake, body comparison, hormones and glucose tolerance. Brain Res 957:144–151

    Article  PubMed  CAS  Google Scholar 

  • Berna M, Ackermann B, Ruterbories K, Glass S (2002) Determination of olanzapine in human blood by liquid chromatography–tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 767:163–168

    Article  PubMed  CAS  Google Scholar 

  • Breier AF, Malhotra AK, Su TP, Pinals DA, Elman I, Adler CM, Lafargue RT, Clifton A, Pickar D (1999) Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response. Am J Psychiatry 156:294–298

    PubMed  CAS  Google Scholar 

  • Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM (1999) Olanzapine. Pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet 37:177–193

    Article  PubMed  CAS  Google Scholar 

  • Crawford AM, Beasley CM Jr, Tollefson GD (1997) The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations. Schizophr Res 26:41–54

    Article  PubMed  CAS  Google Scholar 

  • Cropley J, Gibson V, Rourke C, Hatcher P, Jones DNC, Reavill C (2003) Pharmacological profile of atypical antipsychotic drugs. J Psychopharmacol S17:A48

    Google Scholar 

  • Cutler AJ (2003) Sexual dysfunction and antipsychotic treatment. Psychoneuroendocrinology 28 (Suppl 1):69–82

    Article  PubMed  CAS  Google Scholar 

  • David SR, Taylor CC, Kinon BJ, Breier A (2000) The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther 22:1085–1096

    Article  PubMed  CAS  Google Scholar 

  • Dickson RA, Glazer WM (1999) Neuroleptic-induced hyperprolactinemia. Schizophrenia research 35 (Suppl):S75–S86

    Article  PubMed  Google Scholar 

  • Fell MJ, Marshall KM, Williams J, Neill JC (2004) Effects of the atypical antipsychotic olanzapine on reproductive function and weight gain in female rats. J Psychopharmacol 18:149–55

    Article  PubMed  CAS  Google Scholar 

  • Fell MJ, Gibson R, McDermott E, Sisodia G, Marshall KM, Neill JC (2005) Investigation into the effects of the novel antipsychotic ziprasidone on weight gain and reproductive function in female rats. Behav Brain Res 160:338–43

    Article  PubMed  CAS  Google Scholar 

  • Goff DC, Posever T, Herz L, Simmons J, Kletti N, Lapierre K, Wilner KD, Law CG, Ko GN (1998) An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacol 18:296–304

    Article  PubMed  CAS  Google Scholar 

  • Goodnick PJ, Rodriguez L, Santana O (2002) Antipsychotics: impact on prolactin levels. Expert Opin Pharmacother 3:1381–1391

    Article  PubMed  CAS  Google Scholar 

  • Gudelsky GA, Koenig JI, Simonovic M, Koyama T, Ohmori T, Meltzer HY (1987) Differential effects of haloperidol, clozapine, and fluperlapine on tuberoinfundibular dopamine neurons and prolactin secretion in the rat. J Neural Transm 68:227–240

    Article  PubMed  CAS  Google Scholar 

  • Haddad PM, Wieck A (2004) Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs 64:2291–2314

    Article  PubMed  CAS  Google Scholar 

  • Halbreich U, Kinon BJ, Gilmore JA, Kahn LS (2003) Elevated prolactin levels in patients with schizophrenia: mechanisms and related adverse effects. Psychoneuroendocrinology 28 (Suppl 1):53–67

    Article  PubMed  CAS  Google Scholar 

  • Hamner M (2002) The effects of atypical antipsychotics on serum prolactin levels. Ann Clin Psychiatry 14:163–173

    Article  PubMed  Google Scholar 

  • Heykants J, Huang ML, Mannens G, Meuldermans W, Snoeck E, Van Beijsterveldt L, Van Peer A, Woestenborghs R (1994) The pharmacokinetics of risperidone in humans: a summary. J Clin Psychiatry 55 (Suppl):13–17

    PubMed  Google Scholar 

  • Huang ML, Van Peer A, Woestenborghs R, De Coster R, Heykants J, Jansen AA, Zylicz Z, Visscher HW, Jonkman JH (1993) Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. Clin Pharmacol Ther 54:257–268

    Article  PubMed  CAS  Google Scholar 

  • Kalinichev M, Rourke C, Daniels AJ, Grizzle MK, Britt CS, Ignar DM, Jones DNC (2005) Characterisation of olanzapine-induced weight gain and effect of aripiprazole vs olanzapine on body weight and prolactin secretion in female rats. Psychopharmacology. (online DOI: 10.1007/s00213-005-0081-9)

  • Kapur S, Remington G (2001) Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia. Annu Rev Med 52:503–517

    Article  PubMed  CAS  Google Scholar 

  • Kapur S, Langlois X, Vinken P, Megens AA, De Coster R, Andrews JS (2002) The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood–brain disposition: a pharmacological analysis in rats. J Pharmacol Exp Ther 302:1129–1134

    Article  PubMed  CAS  Google Scholar 

  • Kinon BJ, Gilmore JA, Liu H, Halbreich UM (2003) Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials. Psychoneuroendocrinology 28 (Suppl 2):69–82

    Article  PubMed  CAS  Google Scholar 

  • Kleinberg DL, Davis JM, De Coster R, Van Baelen B, Brecher M (1999) Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychopharmacol 19:57–61

    Article  PubMed  CAS  Google Scholar 

  • Mattheij JA, Swarts JJ (1978) Circadian variations in the plasma concentration of prolactin in the adult male rat. J Endocrinol 79:85–89

    Article  PubMed  CAS  Google Scholar 

  • Meaney AM, Smith S, Howes OD, O'Brien M, Murray RM, O'Keane V (2004) Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia. Br J Psychiatry 184:503–508

    Article  PubMed  CAS  Google Scholar 

  • Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 25:233–255

    PubMed  CAS  Google Scholar 

  • Meltzer HY, Goode DJ, Schyve PM, Young M, Fang VS (1979) Effect of clozapine on human serum prolactin levels. Am J Psychiatry 136:1550–1555

    PubMed  CAS  Google Scholar 

  • Olfson M, Mechanic D, Hansell S, Boyer CA, Walkup J, Weiden PJ (2000) Predicting medication noncompliance after hospital discharge among patients with schizophrenia. Psychiatr Serv 51:216–222

    Article  PubMed  CAS  Google Scholar 

  • Rourke C, Starr KR, Jones DNC (2004) The effect of acute and chronic administration of olanzapine on prolactin levels in rats. J Psychopharmacol S18

  • Serretti A, De Ronchi D, Lorenzi C, Berardi D (2004) New antipsychotics and schizophrenia: a review on efficacy and side effects. Curr Med Chem 11:343–358

    Article  PubMed  CAS  Google Scholar 

  • Sobrinho LG (1998) Emotional aspects of hyperprolactinemia. Psychother Psychosom 67:133–139

    Article  PubMed  CAS  Google Scholar 

  • Stanniland C, Taylor D (2000) Tolerability of atypical antipsychotics. Drug Safety 22:195–214

    Article  PubMed  CAS  Google Scholar 

  • Tollefson GD, Beasley CM Jr, Tran PV, Street JS, Krueger JA, Tamura RN, Graffeo KA, Thieme ME (1997) Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am J Psychiatry 154:457–65

    PubMed  CAS  Google Scholar 

  • Turrone P, Kapur S, Seeman MV, Flint AJ (2002) Elevation of prolactin levels by atypical antipsychotics. Am J Psychiatry 159:133–135

    Article  PubMed  Google Scholar 

  • Yamada Y, Ohno Y, Nakashima Y, Fukuda M, Takayanagi R, Sato H, Tsuchiya F, Sawada Y, Iga T (2002) Prediction and assessment of the extrapyramidal side effects induced by risperidone based on dopamine D2 receptor occupancy. Synapse 46: 32–37

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Claire Rourke

    Present address: GSK Centre for Research in Cognitive and Neurodegenerative Disorders, Biopolis @ One-North, 11 Biopolis Way, The Helios Building #03-01/02, Singapore, 138667, Singapore

Authors and Affiliations

  1. Schizophrenia & Bipolar Disorders, In Vivo Neurobiology, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline plc, New Frontiers Science Park, Third Ave., CM19 5AW, Harlow, Essex, UK

    Claire Rourke, Kathryn R. Starr, Charlie Reavill & Declan N.C. Jones

  2. Drug Metabolism & Pharmacokinetics, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline plc, Park Road, Ware, Hertfordshire, SG12 0DP, UK

    Sue Fenwick & Kim Deadman

Authors
  1. Claire Rourke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathryn R. Starr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Charlie Reavill
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sue Fenwick
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kim Deadman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Declan N.C. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claire Rourke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rourke, C., Starr, K.R., Reavill, C. et al. Effects of the atypical antipsychotics olanzapine and risperidone on plasma prolactin levels in male rats: a comparison with clinical data. Psychopharmacology 184, 107–114 (2006). https://doi.org/10.1007/s00213-005-0230-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-0230-1

Keywords

Search

Navigation