Nuevos fármacos antiasmáticos: inhibición selectiva de isoenzimas de la fosfodiesterasa

Resumen

La identificación de la fosfodiesterasa de nucleótidos cíclicos (PDE), enzima responsable de la destrucción del AMPc y el GMPc intracelular, como punto de acción para las metilxantinas ha originado una creciente actividad investigadora en este campo. Esto ha tenido como resultado la caracterización de múltiples isoenzimas de PDE (PDE1 a PDE 9), su distribución tisular específica, y el descubrimiento y desarrollo de fármacos inhibidores selectivos para algunos de estos iosenzimas.

La disponibilidad de los fármacos inhibidores selectivos de isoenzimas de PDE ha permitido estudios experimentales in vitro e in vivo, cuyo fin era determinar su valor potencial como fármacos antiasmáticos. Aunque la investigación básica está siendo muy importante, la mayoría de los fármacos inhibidores selectivos de PDE están empezando a someterse a ensayos clínicos para valorar su utilidad en el tratamiento de esta patología. La investigación futura debe dirigirse a conocer mejor la distribución tisular de la PDE y su papel en la fisiopatología, así como para desarrollar mejores (mas selectivas) moléculas inhibidoras de la fosfodiesterasa.

Palabras clave: Asma.- Isoenzimas fosfodiesterasa.- Músculo liso vías aéreas.- Células inflamatorias.

Abstract

The identification of cyclic nucleotide phosphodiesterase (PDE), the enzyme responsible for the intracellular degradation of cAMP and cGMP, as the target for methyxanthines has given rise to a reserch effort resulting in the characterization of multiple PDE isoenzymes (PDE 1 to PDE 9), their specific tissular distribution and development of selective inhibitors for some of these isoenzymes. This bioavailability of theese selective PDE isoenzyme inhibitors has permitted studies with regard to their potential value as antiasthmatic drugs. Although the basic research is being intensive, most of the selective PDE isoenzyme inhibitors are beginning to be subjected to clinical trials to asses their usefulness in the treatment of this pathology. Future research should be aimed at ascertaining the tissular distribution of the PDEs and their role in physiophathology, as well as at developing supraselective phosphodiesterase inhibitors. The identification of cyclic nucleotide phosphodiesterase (PDE), the enzyme responsible for the intracellular degradation of cAMP and cGMP, as the target for methyxanthines has given rise to a reserch effort resulting in the characterization of multiple PDE isoenzymes (PDE 1 to PDE 9), their specific tissular distribution and development of selective inhibitors for some of these isoenzymes.

This bioavailability of theese selective PDE isoenzyme inhibitors has permitted studies with regard to their potential value as antiasthmatic drugs. Although the basic research is being intensive, most of the selective PDE isoenzyme inhibitors are beginning to be subjected to clinical trials to asses their usefulness in the treatment of this pathology. Future research should be aimed at ascertaining the tissular distribution of the PDEs and their role in physiophathology, as well as at developing supraselective phosphodiesterase inhibitors.

Keywords: Asthma.- Phosphodiesterase isoenzymes.- Arways smooth muscle.- Inflamatory cells.