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  • Title: Barbiturate enhancement of GABA-mediated inhibition and activation of chloride ion conductance: correlation with anticonvulsant and anesthetic actions.
    Author: Schulz DW, Macdonald RL.
    Journal: Brain Res; 1981 Mar 23; 209(1):177-88. PubMed ID: 6260300.
    Abstract:
    The anesthetic-sedative barbiturate pentobarbital (PB) and the anticonvulsant barbiturate phenobarbital (PhB) were applied to mammalian spinal cord neurons in primary dissociated cell culture to assess their effects on: (1) postsynaptic GABA-responses; (2) paroxysmal activity produced by the convulsant bicuculline; (3) resting membrane properties; and (4) spontaneous neuronal activity. The results demonstrated that: (1) anticonvulsant actions occurred at barbiturate concentrations which augmented GABA-responses; (2) anesthetic actions occurred at barbiturate concentrations which produced direct increases in chloride conductance; (3) both anticonvulsant and anesthetic actions occurred at clinically relevant concentrations; and (4) concentrations of PhB, but not PB, which produced GABA-augmentation and direct conductance changes were widely separated. These findings support the hypotheses that augmentation of GABA-mediated inhibition and possibly reduction of glutamate (GLU)-mediated excitation form the basis at least in part for barbiturate anticonvulsant action and that addition of direct increases in chloride conductance to augmentation of GABA-mediated inhibition and reduction of GLU-mediated excitation may partially underlie anesthetic-sedative barbiturate action.
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