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British Journal of Anaesthesia, Vol 77, Issue 3 385-386, Copyright © 1996 by The Board of Management and Trustees of the British Journal of Anaesthesia


LABORATORY INVESTIGATIONS

I.v. anaesthetic agents do not interact with the verapamil binding site on L-type voltage-sensitive Ca2+ channels

K. Hirota and D. G. Lambert
University Department of Anaesthesia, Leicester Royal Infirmary, Leicester LE1 5WW

In this study we have examined if the i.v. anaesthetic agents thiopentone, pentobarbitone, ketamine, etomidate, propofol and alphaxalone interact with the verapamil binding site on L-type voltage- sensitive Ca2+ channels in rat cerebrocortical membranes. Binding assays were performed in 1 ml volumes of Tris HCl 50 mmol litre-1, pH 7.4, for 90 min at 20 degrees C, with cerebrocortical membranes (200 micrograms of protein), the verapamil binding sites of which were radiolabelled with [3H]verapamil. Non-specific binding was defined in the presence of verapamil 10(-6) mol litre-1. The interaction of i.v. anaesthetics was determined by displacement of [3H]verapamil 0.2 nmol litre-1. The mean concentrations of anaesthetic producing 25% inhibition of specific binding (corrected for the competing mass of [3H]verapamil), K25, were (mmol litre-1): thiopentone 0.68 (SEM 0.14); pentobarbitone 1.22 (0.13); propofol 0.66 (0.10); etomidate 0.24 (0.03); alphaxalone 0.19 (0.02); and ketamine 0.75 (0.04). These concentrations exceeded those seen during anaesthesia and suggest that the neuronal verapamil binding site may not be an important target for i.v. anaesthetic agents.
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R. Lingamaneni and H. C. Hemmings Jr
Differential interaction of anaesthetics and antiepileptic drugs with neuronal Na+ channels, Ca2+ channels, and GABAA receptors
Br. J. Anaesth., February 1, 2003; 90(2): 199 - 211.
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