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Comentario sobre "Disfunción del control respiratorio y de la temperatura corporal tras la inhibición aguda de las
Stefan Löffler1, Jochen Körber, Udo Nubbemeyer
1Department of Psychiatry and Psychotherapy, Clinic Offenbach, Teaching Hospital of Goethe University, D-63069 Offenbach, Germany. stefloeffler@t-online.de
Science (New York, N.Y.)
|August 11, 2012
Resumen
La clozapina-N4-óxido (CNO) no es biológicamente inerte, al contrario de las suposiciones anteriores. Sus productos de conversión pueden interferir con los efectos previstos de los receptores de diseño activados exclusivamente por fármacos de diseño (DREADD).
Área de la Ciencia:
- Farmacología Farmacología.
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Los receptores de diseño activados exclusivamente por fármacos de diseño (DREADD) son herramientas ampliamente utilizadas en la investigación en neurociencias.
- La clozapina-N4-óxido (CNO) se emplea comúnmente como el ligando activador para DREADDs, particularmente aquellos basados en el receptor muscarínico M4.
- Estudios anteriores han considerado en gran medida que el CNO es un compuesto biológicamente inerte.
Objetivo del estudio:
- Para investigar la actividad biológica y el destino metabólico de la clozapina-N4-óxido (CNO).
- Para determinar si el CNO o sus metabolitos pueden afectar a los sistemas biológicos independientemente de la activación de DREADD.
- Reevaluar el supuesto de la inercia del CNO en la investigación de DREADD.
Principales métodos:
- Análisis de las propiedades de ciclo redox del CNO.
- Evaluación de la permeabilidad de la membrana celular del CNO y sus metabolitos.
- Experimentos in vitro e in vivo para detectar efectos biológicos no deseados de las CNO.
Principales resultados:
- CNO se somete a un ciclo redox con clozapina, lo que indica una actividad biológica potencial.
- CNO y sus productos de conversión exhiben permeabilidad de la membrana celular.
- La evidencia sugiere que los metabolitos de CNO pueden socavar los efectos mediados por DREADD, desafiando la noción de activación selectiva de DREADD.
Conclusiones:
- La clozapina-N4-óxido (CNO) no es un ligando biológicamente inerte.
- La actividad biológica y los productos metabólicos del CNO pueden interferir con los experimentos DREADD.
- Los investigadores deben tener cuidado al usar CNO para estudios DREADD debido a los posibles efectos de confusión.
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