Psychopharmacology

, Volume 216, Issue 4, pp 451–473

Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties

Authors

    • NeuroAct Communication
  • Mark S. Kleven
    • Biousian Biosystems, Inc
Review

DOI: 10.1007/s00213-011-2247-y

Cite this article as:
Newman-Tancredi, A. & Kleven, M.S. Psychopharmacology (2011) 216: 451. doi:10.1007/s00213-011-2247-y

Abstract

Rationale

There is increasing interest in antipsychotics intended to manage positive symptoms via D2 receptor blockade and improve negative symptoms and cognitive deficits via 5-HT1A activation. Such a strategy reduces side-effects such as the extrapyramidal syndrome (EPS), weight gain, and autonomic disturbance liability.

Objective

This study aims to review pharmacological literature on compounds interacting at both 5-HT1A and D2 receptors (as well as at other receptors), including aripiprazole, perospirone, ziprasidone, bifeprunox, lurasidone and cariprazine, PF-217830, adoprazine, SSR181507, and F15063.

Methods

We examine data on in vitro binding and agonism and in vivo tests related to (1) positive symptoms (e.g., psychostimulant-induced hyperactivity or prepulse inhibition deficit), (2) negative symptoms (e.g., phencyclidine-induced social interaction deficits and cortical dopamine release), and (3) cognitive deficits (e.g., phencyclidine or scopolamine-induced memory deficits). EPS liability is assessed by measuring catalepsy and neuroendocrine impact by determining plasma prolactin, glucose, and corticosterone levels.

Results

Compounds possessing “balanced” 5-HT1A receptor agonism and D2 antagonism (or weak partial agonism) and, in some cases, combined with other beneficial properties, such as 5-HT2A receptor antagonism, are efficacious in a broad range of rodent pharmacological models yet have a lower propensity to elicit EPS or metabolic dysfunction.

Conclusions

Recent compounds exhibiting combined 5-HT1A/D2 properties may be effective in treating a broader range of symptoms of schizophrenia and be better tolerated than existing antipsychotics. Nevertheless, further investigations are necessary to evaluate recent compounds, notably in view of their differing levels of 5-HT1A affinity and efficacy, which can markedly influence activity and side-effect profiles.

Keywords

5-HT1A receptorsD2 receptorsAntipsychoticSchizophreniaAripiprazoleBifeprunoxCariprazineAdoprazineSSR-181507F15063

Copyright information

© Springer-Verlag 2011