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Antipsychotics: Mode of action highlights

Published online by Cambridge University Press:  16 April 2020

C. Höschl ,
J. Horacek ,
M. Kopecek  and
V. Bubeníková-Valesová
C. Höschl
Affiliation:
Prague Psychiatric Centre, Prague, Czech Republic 3rd Medical Faculty of Charles University, Prague, Czech Republic
J. Horacek
Affiliation:
Prague Psychiatric Centre, Prague, Czech Republic 3rd Medical Faculty of Charles University, Prague, Czech Republic
M. Kopecek
Affiliation:
Prague Psychiatric Centre, Prague, Czech Republic 3rd Medical Faculty of Charles University, Prague, Czech Republic
V. Bubeníková-Valesová
Affiliation:
Prague Psychiatric Centre, Prague, Czech Republic

Abstract

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Dopamine D2 receptor blockade is the main mode of antipsychotic action. The optimal occupancy of D2 receptors seems to be crucial to balancing efficacy and adverse effects such as extrapyramidal symptoms or hyperprolactinaemia. Partial D2 receptor agonism, different pre- and postsynaptic D2 receptor antagonism, serotonergic antagonism and modulation, and neurotrophic effects contribute to differentiated antipsychotic efficacy, less side effects, favourable effects on the negative and cognitive symptoms of schizophrenia, etc. In addition, neurotrophic effects of the 2nd generation antipsychotics increase neuronal plasticity and synaptic remodelling in the striatum, in the prefrontal cortex and hippocampus, which may normalise glutamatergic dysfunction and structural abnormalities postulated by the neurodevelopmental disconnection hypothesis of schizophrenia. We demonstrate these mechanisms using various antipsychotics and serotonin manipulations in animal models of schizophrenia (MK-801).

Type
S03. Symposium: Antipsychotics: Mode of Action Highlights
Information
European Psychiatry , Volume 22 , Issue S1: 15th AEP Congress - Abstract book - 15th AEP Congress , March 2007 , pp. S5
Copyright
Copyright © European Psychiatric Association 2007

References

Horáček, J., Bubeníková-Valešová, V., Kopeček, M., Páleníček, T., Dockery, C., Mohr, P., Höschl, C.Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs, 20 2006; 5: 389–40910.2165/00023210-200620050-00004CrossRefGoogle Scholar
Bubeníková, V., Horáček, J., Kožený, J., Platilová, V., Závěšická, V., Höschl, C.The effect of tryptophan depletion on the action of haloperidol in MK-801 trated rats. Eur J Pharmacol 2004; Vol. 5021-2109–11610.1016/j.ejphar.2004.08.034CrossRefGoogle Scholar
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