Carticaine: action of the local anesthetic on myelinated nerve fibres.
Unlike other clinically used local anesthetics, carticaine contains a thiophene ring. Current voltage relations of peak sodium current INa and steady state potassium current IK were measured in voltage clamp experiments on the node of Ranvier of Rana esculenta. The dependence of the maximum sodium conductance on external concnetration of carticaine is described by an apparent dissociation constant KNa = 0.065 mM at pH = 7.3. An apparent dissociation constant KK = 0.147 mM at pH = 7.3 was calculated on the basis of the action of carticaine on the maximum potassium conductance. Similar to other amine local anesthetics, carticaine blocks sodium channels at a lower concentration than potassium channels, but lower concentrations of the thiophene derivative than of the benzene derivatives are needed to block the ionic channels. The partition coefficients in-octanol/Soerensen buffer at pH = 7.35 follow the sequence lidocaine (46)  more than carticaine (17) more than procaine (2). Therefore, the action of these local anesthetics on sodium channels and potassium channels seems not to follow mere lipid solubility properties of the neutral drug. Increasing the pH from 6.3 to 8.3 favoured the neutral drug form and enhanced the block of both ionic channels but the relative reduction of the ionic currents was larger for potassium currents.
D000818:Animals; D001001:Anura; D002355:Carticaine / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D011893:Rana esculenta; D012964:Sodium / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*
D007473:Ion Channels; D013876:Thiophenes; D012964:Sodium; D002355:Carticaine; D011188:Potassium