Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists.

Abstract:

:Antischizophrenic neuroleptic drugs of the diphenylbutylpiperidine class, which includes pimozide, fluspirilene, penfluridol, and clopimozide, inhibit [3H]nitrendipine binding with IC50 values of 13-30 nM. This inhibition involves receptors for the verapamil/prenylamine class of calcium channel antagonists. These diphenylbutylpiperidines also inhibit potassium-induced calcium-dependent contractions of rat vas deferens at concentrations of 40-350 nM. Other phenothiazine and butyrophenone neuroleptics lack such potent calcium-antagonist actions. Diphenylbutylpiperidines also differ from other neuroleptics in their ability to relieve negative symptoms of schizophrenia, such as emotional withdrawal, as well as the positive symptoms which respond to all neuroleptics. We suggest that these unique antischizophrenic actions are related to a blockade by diphenylbutylpiperidines of voltage-operated calcium channels.

authors

Gould RJ,Murphy KM,Reynolds IJ,Snyder SH

doi

10.1073/pnas.80.16.5122

subject

Has Abstract

pub_date

1983-08-01 00:00:00

pages

5122-5

issue

16

eissn

0027-8424

issn

1091-6490

journal_volume

80

pub_type

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