No evidence for specific opioid effects on batrachotoxin-modified sodium channels from human brain synaptosomes.
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) but 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.
Frenkel
C
C
Klinik für Anästhesiologie und spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, Germany.
Gerhard
A
A
Wartenberg
H C
HC
Rehberg
B
B
Urban
B W
BW
D015760:Alfentanil / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D001496:Batrachotoxins / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D004594:Electrophysiology; D006801:Humans; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D011957:Receptors, Opioid / Q000187:drug effects*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000701:Analgesics, Opioid; D001496:Batrachotoxins; D008051:Lipid Bilayers; D011957:Receptors, Opioid; D015222:Sodium Channels; D015760:Alfentanil