• DOI:10.1007/s00213-011-2247-y
• Corpus ID: 5835943

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

@article{NewmanTancredi2011ComparativePO,
  title={Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties},
  author={Adrian Newman-Tancredi and Mark S. Kleven},
  journal={Psychopharmacology},
  year={2011},
  volume={216},
  pages={451-473}
}

• A. Newman-Tancredi, M. Kleven
• Published 11 March 2011
• Psychology
• Psychopharmacology

RationaleThere 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.ObjectiveThis 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.MethodsWe 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.ResultsCompounds 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.ConclusionsRecent 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.