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British Journal of Anaesthesia, Vol 81, Issue 2 249-250, Copyright © 1998 by The Board of Management and Trustees of the British Journal of Anaesthesia

SHORT COMMUNICATIONS

Aging decreases the sensitivity of the GABA carrier to propofol and etomidate

H. Keita, S. Lasocki, D. Henzel-Rouelle, J. M. Desmonts and J. Mantz
Institut National de la Sante et de la Recherche Medicale (INSERM), U 408, Faculte Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France

The influence of aging on the pharmacodynamics of anaesthetic agents in the central nervous system remains poorly understood. As alpha- aminobutyric acid (GABA)-mediated neurotransmission appears to be an important target for anaesthetics in the brain, we hypothesized that aging could alter the sensitivity of the GABA carrier to anaesthetics. We have examined the effects of etomidate and propofol on the uptake of [3H]-GABA (5 min, 37 degrees C) into striatal synaptosomes of rats aged 2, 18 and 24 months. In 2-month-old rats, [3H]-GABA uptake was inhibited by nipecotic acid, a competitive inhibitor of the GABA carrier (IC50 = 3.6 SD 0.3 microM). Etomidate and propofol markedly reduced the activity of the GABA carrier, with IC50 values 58 (SD 3) and 46 (SD 3) microgramsmol litre-1, respectively. Aging increased IC50 values for these anaesthetics. Nipecotic acid was unaffected. These data suggest that aging selectively alters the action of etomidate and propofol in the mammalian CNS.
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