Overview
Alomone Labs Penfluridol inhibits T-type CaV3.2 channels heterologously expressed in Xenopus oocytes.A. Time course of current reversible inhibition by 1 µM Penfluridol (#P-135). Currents were elicited by a voltage ramp from a holding potential of -100 mV to 60 mV (60 ms) delivered every 10 seconds. B. Example traces of current response to voltage ramp stimulation before and during 1 µM Penfluridol application.
Penfluridol was first synthesized in 1968. It is a white micro-crystalline tertiary amine, only slightly soluble in water. Penfluridol is a member of the potent and long-acting series of diphenylbutyl piperidine (DPBPs) neuroleptics of which pimozide is the prototype1. This drug is an effective long acting neuroleptic, particularly useful in the maintenance therapy of schizophrenic patients2.
Penfluridol is not subtype-selective on the three neuronal T-type Ca2+ channels. The potency of DPBPs as T-type Ca2+ channel antagonists parallels their potency as D2 receptor antagonists3.
Blockage of other channels has not been studied in detail, although it should be noted that these drugs are also potent blockers of K+ channels and bind with subnanomolar affinity to L-type channels4.
Penfluridol blocked T-type currents in adrenal zona fasciculata cells with an IC50 of 224 nM. It was also 10-fold more selective for T-type low voltage activated (LVA) currents over L- and N-type high voltage activated (HVA) currents, as 500 nM penfluridol inhibited 82% of the LVA current but only 20% of the HVA4.
In the rat striatum and cortex, IC50s for [3H]nitrendipine displacement were 16 nM and 30nM, respectively5.
In the whole-cell version of the patch-clamp technique, when step depolarizations were applied at 0.1 Hz from a holding potential of -80 mV, with 10 mM Ca2+ as the charge carrier, the DPBP penfluridol inhibited T-type current with an IC50 of 224 nM (using neural crest-derived rat and human thyroid C cell lines)6, while in adrenal zona fasciculate IC50 is 300 nM3.
