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  • Title: Site of action and active form of procaine in squid giant axons.
    Author: Narahashi T, Frazier DT.
    Journal: J Pharmacol Exp Ther; 1975 Sep; 194(3):506-13. PubMed ID: 240018.
    Abstract:
    The active form of procaine and its, site of action on the nerve membrane have been studied in intact and internally perfused squid giant axons. Voltage clamp techniques were employed to measure the masimum values for peak sodium conductance and for steady-state potassium conductance as an index of activity. Changes in internal pH between 7 and 8 do not influence the blocking potency of procaine applied internally. This result, when compared to theoretical curves, is only compatible with the notion that the charged form of procaine present inside is the active form. If one momentarily arrests internal perfusion during an experiment in which procaine is being applied externally, the conductance block is significantly potentiated. When procaine is applied simultaneously to both external and internal phases, most of the block can be reversed by washing out the inside at a time when the outside is still being perfused with procaine. If one reverses this procedure, very little recovery is noted with removal of procaine from the external phase. The rate of recovery from the procaine blockage is much faster in internally perfused axons. These three observations support the notion that procaine acts from inside the nerve membranes. It is concluded that procaine, as other lidocaine derivatives studied previously, acts from the internal nerve membrane surface in the charged form.
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