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2003, Número 5

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Salud Mental 2003; 26 (5)


Avances recientes en la investigación de los mecanismos celulares de acción de los disolventes de abuso.

Páez-Martínez N, López-Rubalcava C, Cruz SL

Idioma: Español
Referencias bibliográficas: 57
Paginas: 43-50
Archivo PDF: 222.08 Kb.


RESUMEN

El presente trabajo es una revisión de los hallazgos recientes acerca de los mecanismos de acción de disolventes orgánicos industriales en el nivel molecular. Se incluyen los efectos de algunos de los principales disolventes de abuso sobre los receptores a glutamato del tipo NMDA y no-NMDA, receptores a GABAA, glicina, 5-HT3, nicotínicos y muscarínicos, así como sobre el sistema de neurotransmisión mesolímbico dopaminérgico y sobre la formación de especies reactivas de oxígeno. La mayoría de los estudios de los efectos de disolventes sobre receptores ionotrópicos se obtuvo utilizando receptores recombinantes, expresados en ovocitos de ranas Xenopus laevis, y registrando las corrientes iónicas a través de ellos por medio de la técnica de fijación de voltaje de dos electrodos. Otros estudios se realizaron en cultivos neuronales. Los datos obtenidos pueden resumirse de la siguiente manera: A) El benceno, el tolueno, el m-xileno, el etil-benceno, el propil-benceno y el 1,1,1-triloroetano (TCE) inhiben los receptores NMDA; con mayor potencia a los receptores del subtipo NR1/2B que a los del subtipo NR1/2A. La inhibición es completa, reversible y dependiente de la concentración del disolvente y no se presenta para otros tipos de receptores glutamatérgicos como los no-NMDA (AMPA y kainato). B) El tolueno, el TCE y el tricloroetileno aumentan la función de los receptores GABAérgicos del subtipo GABAA, de los receptores a glicina y de los receptores a la serotonina del subtipo 5-HT3. C) El tolueno inhibe con diferente potencia a distintos subtipos de receptores colinérgicos nicotínicos; de ellos, el más sensible el α4Β2 . En cuanto a sus efectos sobre los receptores muscarínicos, el tolueno también posee actividad antagonista aunque con menor potencia que la observada para antagonizar a los receptores nicotínicos. Los estudios enfocados a los efectos del tolueno sobre canales iónicos activados por voltaje han demostrado que este disolvente inhibe las corrientes de calcio inducidas por la depolarización de células de feocromocitoma y que también actúa como antagonista de los canales cardiacos de sodio. Es importante señalar que las concentraciones en que los disolventes ejercen sus efectos in vitro son relevantes para el consumo humano en condiciones de intoxicación. En conjunto, estos estudios demuestran que los disolventes tienen un mecanismo de acción complejo similar al descrito para el etanol. Sin embargo, un estudio comparativo muestra que el tolueno es de 10 a 1000 veces más potente que el etanol. Por otra parte, la formación de radicales libres parece ser un mecanismo común a varios disolventes y se ha propuesto que pudiera cumplir un papel importante en algunos de sus efectos crónicos.


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