Activation of sodium transport and intracellular sodium lowering by the neuroleptic drug chlorpromazine.
Chlorpromazine (CPZ), a commonly used antipsychotic drug, at high concentration was found to reduce significantly the sodium content of both rat (Rattus norvegicus) and toad (Bufo marinus) liver cells. This reduction in intracellular sodium was demonstrated using 22Na+ flux and measurement of cell sodium content. The results suggest that the sodium-lowering effect of CPZ stemmed from a stimulation of sodium transport rather than from an inhibition of sodium influx (i.e., sodium channels), cell damage, or Na+:Na+ exchange. CPZ was found to interfere with the binding of ouabain to the sodium pump, although a simple reduction in sodium pump inhibition did not account for the sodium-lowering effect. CPZ was able to negate the effects of monensin, a sodium ionophore, 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.
Else
P L
PL
Department of Biomedical Science, University of Wollongong, N.S.W., Australia.
Mansfield
K
K
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002025:Bufonidae; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*
D014150:Antipsychotic Agents; D010042:Ouabain; D008985:Monensin; D012964:Sodium; D002746:Chlorpromazine