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Review
. 2006;8(3):303-9.
doi: 10.31887/DCNS.2006.8.3/broth.

Contributions of molecular biology to antipsychotic drug discovery: promises fulfilled or unfulfilled?

Bryan L Roth  1
Affiliations
Review

Contributions of molecular biology to antipsychotic drug discovery: promises fulfilled or unfulfilled?

Bryan L Roth. Dialogues Clin Neurosci. 2006.

Abstract
in English, Spanish, French

This review summarizes the various conceptual paradigms for treating schizophrenia, and indicates how molecular biology and drug discovery technologies can accelerate the development of new medications. As yet, there is no convincing data that a crucial druggable molecular target exists which, if targeted, would yield medications with efficacies greater than any currently available. It is suggested, instead, that drugs which interact with a multiplicity of molecular targets are likely to show greater efficacy in treating the core symptoms of schizophrenia.

Esta revisión resume los diverses paradigmas conceptuales que existen para el tratamiento de la esquizofrenia e indica cómo la biología molecular y las tecnologías para el descubrimienio de fármacos pueden acelerar el desarrollo de nuevos medicamentos, Aun no se dispone de información convincente acerca de la exisiencia de una molécula específica, que pueda transformarse en un medicamento, y que de encontrarse pueda dar origen a fármacos más eficaces que cualquiera de los actualmente disponibles. Se sugiere, en cambio, que es probable que fármacos que interactúan con una multiplicidad de blancos moleculares muestren mayor eficacia en el tratamiento de los síntomas centrales de la esquizofrenia.

Cet article résume les différents modèles conceptuels de traitement de la schizophrénie et montre comment la biologie moléculaire et les technologies de découverte des médicaments peuvent accélérer le développement de nouveaux traitements. Nous ne disposons pas encore de données convaincantes sur l'existence d'une molécule décisive, transformable en médicament qui, si elle était choisie, déboucherait sur des traitements plus efficaces que ceux disponibles actuellement. Il est plutôt suggéré que les médicaments interagissant avec les nombreuses cibles moléculaires seraient plus efficaces dans le traitement des symptômes clés de la schizophrénie.

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Figures

Figure 1
Figure 1. Schizophrenia susceptibility genes are localized in overlapping neuronal pathways. Shown in diagrammatic form are the presumed localizations of various schizophrenia susceptibility gene products in a model synapse in the prefrontal cortex. As shown, a typical pyramidal neuron fiber receives inputs from dopaminergic, serotonergic, glutamatergic, and GABA-ergic neurons. The various susceptibility genes indicated may modulate pre- or postsynaptic glutamatergic functioning. Antipsychotic drugs mainly affect biogenic amine receptor activities which may be either pre- or postsynaptic in nature. GABA, γ-aminobutyric acid
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