Inhibition of the Activity of Phosphoinositide-Specific Phospholipase C Isozymes by Antipsychotics and Antidepressants

To elucidate the effect of antipsychotics and antidepressants on phosphoinositide(Pl) second massenger system, we studied the dose-dependent inhibition of the phosphoinositide-specific phospholipase C(PLC) isozymes, ${\beta}_1,\;{\gamma}_1$ and${\delta}_1,$ by fluphenazine and haloperidol as antipsychotics, and amitriptyline, maprotiline and mianserin as antidepressants. All the antipsychotics and antidepressants tested showed inhibition on at least one of the PLC isozymes with $IC_{50}$ at the concentration between 25 and $250 {\mu}M.$ Maprotiline, mianserin and amitriptyline inhibited 80 to 90% of the activities of all three PLC isozymes at the concentration of $250{\mu}M,$ while haloperidol and fluphenazine inhibited PLC ${\beta}_1$ and${\gamma}_1$ But baclofen didn't inhibit any PLC isozyme. These results suggested that PLC isozymes are inhibited by antipsychotics and antidepessants even though the concentration is high, and these drugs may affect PI signal transduction system by direct inhibition of PLC isozymes.