ACTIVATION OF SODIUM-TRANSPORT AND INTRACELLULAR SODIUM LOWERING BY THE NEUROLEPTIC DRUG CHLORPROMAZINE

Chlorpromasine (CPZ), a commonly used antipsychotic drug, at high conc entration was found to reduce significantly the sodium content of both rat (Rattus norvegicus) and toad (Bufo marinus) liver cells. This red uction in intracellular sodium was demonstrated using Na-22(+) flux an d measurement of cell sodium content. The results suggest that the sod ium-lowering effect of CPZ stemmed from a stimulation of sodium transp ort rather than from an inhibition of sodium influx (i.e., sodium chan nels), cell damage, or Na+:Na+ exchange. CPZ was found to interfere wi th the binding of ouabain to the sodium pump, although a simple reduct ion in sodium pump inhibition did not account for the sodium-lowering effect. CPZ was able to negate the effects of monensin, a sodium ionop hore, suggesting a substantial capacity to activate sodium transport. The intracellular sodium-lowering action of CPZ through the activation of sodium transport represents a new property previously undescribed for this drug. (C) 1997 Elsevier Science Inc.