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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Acetanilides: effects on invertebrate neurons correlated with analgesic activity in vertebrates.

Identified neurons in the buccal ganglion of the marine mollusc Navanax inermis were used to examine the effects of acetanilides on neuronal membrane properties. Acetanilides increased the membrane potential and conductance of these neurons in a dose-dependent, reversible manner. These events would have the effect of decreasing membrane excitability. Acetanilides increased the slope of the curve of membrane potential as a function of log [K+]o from 33 to 58 mV decade change in [k+]o and decreased the transient depolarization observed upon reducing [Cl]o. These results indicate that acetanilides increase membrane potential and conductance by increasing the potassium conductance of the membrane relative to the chloride conductance. The variation in membrane potential as a function of external alkali-cation concentrations was used an as indirect measure of alkali-cation permeability. Acetanilides altered the relative cation permeability from Rb (1.25) greater than K (1.0) greater than Cs (0.60) greater than NaequalsLi (0.07) to K (1.0) greater than Rb (0.71) greater than Cs (0.31) greater than NaequalsLi (0.00). This shift in relative cation permeability is interpreter, in terms of Eisenman's theory of membrane permselectivity, as indicating that acetanilides increase the anionic field strength of the membrane. The ability of acetanilides to increase membrane potential or alter permselectivity is directly correlated with octanol-water partition coefficient (r equals 0.96), indicating that hydrophobicity per se can account for almost all of the activity. Steric factors are unimportant. Analysis of published experiments on acetanilide analgesia in mice reveals that hydrophobicity can also account for much of the activity in that system. Results obtained in the molluscan system may thus provide insight into the ionic, biophysical and physicochemical mechanisms underlying acetanilide-induced analgesia.[1]


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