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

• Published in: Neuroscience letters Vol. 229; no. 1; pp. 41 - 44
• Main Authors: Frenkel, Christian, Gerhard, Alexander, Wartenberg, Hans C, Benno Rehberg, Urban, Bernd W
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 20.06.1997; Elsevier
• Subjects: Alfentanil; Alfentanil - pharmacology; Anaesthesia; Analgesics; Analgesics, Opioid - pharmacology; Batrachotoxins - pharmacology; Biological and medical sciences; Brain Chemistry - drug effects; Electrophysiology; Human brain; Humans; In Vitro Techniques; Lipid bilayer; Lipid Bilayers; Mechanism of action; Medical sciences; Membrane Potentials - physiology; Neuropharmacology; Opioid; Patch-Clamp Techniques; Pharmacology. Drug treatments; Receptors, Opioid - drug effects; Sodium Channels - drug effects; Sodium Channels - metabolism; Synaptosomes - drug effects; Synaptosomes - metabolism; Voltage-clamp; Anaesthesia; Voltage-clamp; Alfentanil; Opioid; Human brain; Lipid bilayer; Mechanism of action; Human; Synaptosome; Sodium; Central nervous system; Opiates; Ionic channel; Narcotic analgesic; Brain (vertebrata)
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(97)00408-4

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 EC 50 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.