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


OBJECTIVE
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.
Rourke
Claire
C
Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline plc, New Frontiers Science Park, Third Ave., CM19 5AW Harlow, Essex, UK. claire.2.rourke@gsk.com
Starr
Kathryn R
KR
Reavill
Charlie
C
Fenwick
Sue
S
Deadman
Kim
K
Jones
Declan N C
DN
D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001569:Benzodiazepines / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D008297:Male; D000077152:Olanzapine; D011388:Prolactin / Q000097:blood*; D051381:Rats; D018967:Risperidone / Q000493:pharmacokinetics / Q000494:pharmacology*; D013997:Time Factors; D014018:Tissue Distribution
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D011388:Prolactin; D018967:Risperidone; D000077152:Olanzapine