Penfluridol
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 prototype. This drug is an effective long acting neuroleptic, particularly useful in the maintenance therapy of schizophrenic patients.
Penfluridol is not subtype-selective on the three neuronal T-type Ca+2 channels. The potency of DPBPs as T-type Ca+2 channel antagonists parallels their potency as D2 receptor antagonists.
Block 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 channels.
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 HVA.
In the rat striatum and cortex IC50's for [3H]nitrendipine displacement were 16 nM and 30nM, respectively.
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), while in adrenal zona fasciculate IC50 is 300 nM.
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