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

Antipsychotic pimozide is a potent Ca2+ channel blocker in heart.

The diphenylbutylpiperidine (DPBP) antipsychotic pimozide was identified as a potent new Ca2+ channel antagonist in heart. In whole-cell patch-clamp experiments, pimozide blocked Ca2+ current through L type channels of rat ventricular myocytes, in a voltage-dependent manner. At holding potentials positive to -40 mV, approximately 90% of current was blocked by 200 nM pimozide. Nearly half of this block, 48 +/- 5% (mean +/- SE, n = 5), was relieved by 5-min hyperpolarization to -100 mV. In quin2-loaded myocytes, pimozide blocked 50 mM KCl-induced increases in intracellular Ca2+ concentration [( Ca2+]i) half maximally at a concentration of 75 +/- 15 nM (n = 5). Two other DPBPs, penfluridol and fluspirilene, also blocked the KCl-induced response at similar concentrations. The contractile force of cardiac tissue was also depressed by pimozide. One micromolar pimozide reduced twitch tension in rat papillary muscles by an average of 36 +/- 8% (n = 3). These results demonstrate that the DPBPs comprise a potent new class of Ca2+ antagonists in heart, which will be useful in studying cardiac Ca2+ channels. They also suggest that these agents may have therapeutic value outside the field of psychiatry.[1]

References

  1. Antipsychotic pimozide is a potent Ca2+ channel blocker in heart. Enyeart, J.J., Dirksen, R.T., Sharma, V.K., Williford, D.J., Sheu, S.S. Mol. Pharmacol. (1990) [Pubmed]
 
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