Effects of chlorpromazine and its dihydroxy metabolite on calcium movement and electrical activity in superior cervical ganglia.
Chlorpromazine (CPZ) binding and the binding to isolated guinea pig superior cervical of a toxic metabolite 7,8-dihydroxychlorpromazine (7,8-diOH-CPZ) were studied under resting and potassium-stimulated conditions. Maximal binding occurred more rapidly in high potassium, with binding of CPZ 10 fold higher than that of 7,8-diOH-CPZ. However, in low potassium media 50% of bound CPZ and 60% of 7,8-diOH-CPZ was retained following a 240-min washout procedure. When the washout of the drugs from the tissue was studied, release was found to be more extensive in high potassium washout media. Under resting conditions, at 10 microM CPZ or 7,8-diOH-CPZ, calcium accumulation by ganglia decreased but increased at higher drug concentrations. Calcium (Ca) uptake increased with both drugs in high potassium medium. Ca efflux from the tissue was accelerated by both phenothiazines in a dose-dependent fashion. CPZ blocked ganglionic transmission at 20 microM while 7,8-diOH-CPZ (up to 100 microM) increased ganglionic potential amplitude. Thus CPZ and 7,8-diOH-CPZ differ in binding to ganglia and in effects on ganglionic transmission.
Guzman-Harty
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Tjioe
S A
SA
O'Neill
J J
JJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002746:Chlorpromazine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D011188:Potassium / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
C028819:7,8-dihydroxychlorpromazine; D011188:Potassium; D002118:Calcium; D004229:Dithiothreitol; D002746:Chlorpromazine