Macrokinetic analysis of blockade of NMDA-gated currents by substituted alcohols, alkanes and ethers

Brain Research
Hugh E CriswellGeorge R Breese

Abstract

Volatile hydrocarbon based CNS depressants including short chain alcohols and anesthetics act, in part, by inhibition of the excitatory effect of glutamate at the NMDA receptor. While effects of several of these volatile agents on NMDA-gated currents have been demonstrated, there has been no direct comparison of different chemical classes of CNS depressant drugs on NMDA-gated currents. Here, whole-cell voltage clamp measurements of currents gated by 100 microM NMDA from cultured cerebrocortical neurons were examined in the presence of varying concentrations of the alcohols ethanol and hexanol, the halogenated alcohol trichloroethanol, the halogenated alkane halothane and the halogenated ethers isoflurane and sevoflurane. All drugs tested showed concentration-dependent inhibition of NMDA-gated currents with anesthetic concentrations of each agent producing approximately 30% inhibition of the NMDA-gated current. A rapid-translation perfusion system was used to study the onset and offset kinetics of each of the volatile agents. Onset kinetics for the CNS depressants was similar with tau values near 100 ms. Offset kinetics was more variable with tau ranging from 88.2 ms for ethanol to 221.4 ms for trichloroethanol. These data indic...Continue Reading

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Citations

Feb 1, 2012·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Jun-Gol SongIn Cheol Choi
Oct 16, 2007·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Andrew P HarrisRaymond C Koehler
Jun 27, 2006·Journal of Clinical Anesthesia·Vincenzo FodaleLetterio B Santamaria
May 7, 2009·Experimental Neurology·Cecily E HamillStephen F Traynelis
Jan 18, 2014·BMC Anesthesiology·François-Xavier LapébieBruno François
Apr 20, 2006·The Journal of Pharmacology and Experimental Therapeutics·Junichi OgataR Adron Harris
Aug 28, 2019·Journal of Alzheimer's Disease : JAD·Yuan Tian, Mingrui Song
Jun 9, 2015·European Journal of Anaesthesiology·Danièle Lefebvre-KuntzPierre Schoeffler

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