Anesthetic action of opiates: correlations of lipid solubility and spectral edge.
The ability of opiates to be a complete anesthetic has been assessed in animals. These studies have investigated the serum levels of opiate required to produce a decrease in anesthetic requirement for a concomitantly administered inhalation anesthetic. A linear dose-response relation has been observed between opiate serum level and reduction in anesthetic requirement up to the level of 50% reduction in minimum alveolar anesthetic concentration (MAC). These studies have not demonstrated the production of one MAC anesthesia by the opiates. Recent EEG studies have provided another means of comparing the central nervous system effects of opiates and inhalation anesthetics. The serum levels of several opiates associated with a 50% reduction (IC50 or 50% inhibitory concentration) in maximal spectral edge frequency (SEF) have been reported. The free, unionized serum levels of each opiate at IC50 in humans or 50% MAC reduction in animals are remarkably similar. We calculated brain lipid opiate content at these serum levels using available physiochemical data. The calculated nanogram and molar brain lipid contents of the drugs fell within a 10-fold range while serum levels varied by 5000-fold. This similarity in membrane lipid content in association with EEG and anesthetic effects suggests that opiate "anesthesia" may involve a membrane effect in addition to the well established receptor interaction.
Stone
D J
DJ
Department of Anesthesiology, University of Virginia Medical Center, Charlottesville 22908.
DiFazio
C A
CA
D000769:Anesthesia, Inhalation; D000777:Anesthetics; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004285:Dogs; D004569:Electroencephalography; D006801:Humans; D050356:Lipid Metabolism; D009294:Narcotics / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012995:Solubility
D000777:Anesthetics; D009294:Narcotics