The profound effects of numbing agents

December 11, 2008

A large proteomics study on the brains of newborn mice provides more evidence that numbing drugs often used in obstetric or pediatric medicine can have profound and long-term negative effects, even after minimal exposure.

This study, appearing in the December issue of Molecular and Cellular Proteomics, highlights the delicate state of the developing nervous system and reinforces the use of caution when administering sedatives, anesthetics, and anti-convulsants to pregnant women or infants.

Compounds that either block excitatory NMDA receptors or activate inhibitory GABA receptors in the brain are clinically useful as anesthetics or for treating disorders like seizures and insomnia. However, just like other chemicals that produce similar mind-soothing effects (e.g. alcohol), excessive use can be detrimental -particularly in still-developing individuals.

To examine how far-reaching the physiologic effects of such 'numbing' drugs (sedatives, hypnotics, analgesics) are, Angela Kaindl and colleagues treated 6-day old mice with two doses of either the NMDA receptor blocker dizocilpine or the GABA receptor activator Phenobarbital and then analyzed subsequent changes in brain protein expression.

They observed both acute and sustained effects, with protein changes in the cerebral cortex (the area controlling memory, thought, awareness, and language) evident after just 24 hours, and these changes were still present one week and one month after the one-day drug treatment. The affected proteins are involved in crucial processes like cell growth, cell death, and the formation of neural circuits (In another recent study, the authors were able to confirm that such drug treatment negatively influences learning and memory).

A similar drug dose given to adult mice did not produce such changes, which the authors note clearly shows how susceptible infant brains are compared to adults. Importantly, this study shows that drug overuse on even one occasion (for example, during the delivery procedure) can have long-term implications.
-end-
From the study: "Brief Alteration of NMDA or GABAA Receptor mediated Neurotransmission Has Long Term Effects on the Developing Cerebral Cortex" by Angela M. Kaindl, Andrea Koppelstaetter, Grit Nebrich, Janine Stuwe, Marco Sifringer, Claus Zabel, Joachim Klose and Chrysanthy Ikonomidou

Article link: http://www.mcponline.org/cgi/content/abstract/7/12/2293

Corresponding Author: Angela Kaindl, Dept. of Pediatric Neurology, Charite-Universitätsmedizin Berlin, Germany; Tel: 49-30-450-566112; E-mail: angela.kaindl@charite.de

Note: Dr. Kaindl will be at the Laboratoire de Neurologie du Développement, Paris, until Dec 19, Tel: +33 140 03 19 97

The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

For more information about ASBMB, see the Society's Web site at www.asbmb.org

American Society for Biochemistry and Molecular Biology

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