No evidence for specific opioid effects on batrachotoxin-modified sodium channels from human brain synaptosomes

[摘要] Human central nervous system (CNS) sodium channels modified by batrachotoxin and incorporated inter voltage-clamped lipid bilayers, were exposed to various concentrations of the opioid alfentanil (0.2 - 8.0 mM). Alfentanil caused a concentration-dependent and membrane potential independent reduction of the single channel amplitude and the fractional channel open-time. The weighted computer fit of the dose-response curve yielded a maximal conductance block of 50% with an EC50 of 1.3 mM. These effects occurred at levels beyond clinically relevant human serum/brain levels (0.003 mM) bur within the predicted concentration range using the Meyer-Overton (lipid solubility/anaesthetic potency) correlation. Thus, human CNS sodium channels are probably not a main target site for the clinical effects of alfentanil but they provide a model system to estimate the proportion of the lipophilic interactions contributing to its overall effect. (C) 1997 Elsevier Science Ireland Ltd.

[发布日期] 1997-06-20

[关键词] alfentanil;opioid;anaesthesia;human brain;lipid bilayer;voltage-clamp;mechanism of action