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Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists.
Open accessAbstract
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.
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Citations
Cited by
Shapiro, E. (1989) · Archives of General Psychiatry · doi:10.1001/archpsyc.1989.01810080052006 · Cited by 355
Treatment of the Neuroleptic-Nonresponsive Schizophrenic Patient
Meltzer, H. Y. (1992) · Schizophrenia Bulletin · doi:10.1093/schbul/18.3.515 · Cited by 332
Drug and Neurotransmitter Receptors in the Brain
Snyder, S. H. (1984) · Science · doi:10.1126/science.6322304 · Cited by 273
Self-citationCa 2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen 1
Ray, S. D., Kamendulis, L. M., Gurule, M. W., Yorkin, R. D., & Corcoran, G. B. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.5.8462787 · Cited by 198
TSUTSUI, S., ITAGAKI, S.-I., KAWAMURA, S., HARADA, K.-I., KARAKI, H., DOI, K., & YOSHIKAWA, Y. (2003) · Experimental Animals · doi:10.1538/expanim.52.43 · Cited by 14
Metadata
- Authors
- Gould, R. J., Murphy, K. M., Reynolds, I. J., & Snyder, S. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1983-08
- Volume
- 80
- Issue
- 16
- Pages
- 5122-5125
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1978322781
- Cited by
- 218
- References
- 0
- FWCI
- 11.43
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Gould, R. J., Murphy, K. M., Reynolds, I. J., & Snyder, S. H. (1983). Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.80.16.5122
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
