British Journal of Anaesthesia, Vol 81, Issue 6 932-939, Copyright © 1998 by The Board of Management and Trustees of the British Journal of Anaesthesia
R. Z. Zhan, N. Fujiwara, T. Yamakura, K. Taga, S. Fukuda and K. Shimoji
Although it is known that there are some pharmacological differences
between the structurally similar barbiturates, the underlying mechanism of
action remains unclear. We have compared the effects of thiopental,
thiamylal and phenobarbital on both voltage-gated calcium channels (VGCC)
and N-methyl-D-aspartate (NMDA) receptors in rat hippocampal slices by
determining changes in intracellular calcium ([Ca2+]i). Experiments were
performed in adult rat hippocampal slices perfused with Krebs solution (37
degrees C). Concentrations of [Ca2+]i in the pyramidal cell layer of the
CA1 region were measured using a calcium indicator dye, fura-2. To activate
VGCC and NMDA receptors, slices were exposed to K+ 60 mmol litre-1 (< or
= 60 s) and NMDA 100 microgramsmol litre-1 (30 s), respectively.
Thiopental, thiamylal and phenobarbital were present 5 min before, during
and 1 min after high K+ or NMDA application. Both thiamylal and thiopental
(50-600 microgramsmol litre-1) attenuated the increases in [Ca2+]i produced
by high K+ or NMDA in a concentration-dependent manner, while phenobarbital
50-1000 microgramsmol litre- 1 only slightly attenuated the [Ca2+]i
increase produced by high K+ at concentrations of more than 200
microgramsmol litre-1 and was ineffective on the [Ca2+]i response produced
by NMDA. Although the increases in [Ca2+]i caused by membrane
depolarization with high K+ were reduced equally with thiamylal and
thiopental, thiamylal was more effective in attenuating the increase in
[Ca2+]i produced by NMDA receptor activation than thiopental. We conclude
that the depressant effects of barbiturates on both VGCC and NMDA receptors
varied between agents. Differential inhibition of both VGCC and NMDA
receptors may determine the pharmacological properties of barbiturates and
their ability to protect neurones against ischaemia.
LABORATORY INVESTIGATIONS
Differential inhibitory effects of thiopental, thiamylal and phenobarbital on both voltage-gated calcium channels and NMDA receptors in rat hippocampal slices
Department of Anaesthesiology, Niigata University School of Medicine, 1-757 Asahimachi, Niigata 951-8510, Japan
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