Articles: anesthetics.
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J. Pharmacol. Exp. Ther. · Apr 1980
Structure-activity relations for frequency-dependent sodium channel block in nerve by local anesthetics.
Different local anesthetic drug structures differ significantly in their capabilities for producing frequency (f)-dependent sodium channel block. Voltage-clamped frog myelinated nerve preparations have been utilized in order to investigate structure-activity relations for several modes of local anesthetic drug action, including the kinetics of f-dependent excitability block. ⋯ In addition, f-dependent block increments are greater for drugs of lower lipid solubility, supporting the "modulated drug receptor" hypothesis that intracellular drug forms participate in the open channel binding involved in f-dependent blocking. Finally, molecular size has been shown to be a very important determinant of closed channel block escape rates with smaller drug structures showing faster escape rates from f-dependent increments in channel block.
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In five adult horned sheep long-term cerebro-spinal fluid pressure measurements were carried out before, during and after ten spinal-anaesthetics with the help of a canula which was fixed on the skull. In the lumbar subarachnoid space the pressure-course was recorded also, before and after the injection of local-anaesthetic. The following reproducible phenomena were found: Rapid pressure increase after injection, increase of cardio-respiratory oscillations and in two cases a sharp decrease of pressure after removal of the spinal needle. A connection between this and the cause of postural headache in man is postulated.