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PMID: 6572372 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A unitary mechanism of calcium antagonist drug action.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 80 ·No. 3 ·1983-02-00 ·Pages 860-4

Murphy KM, Gould RJ, Largent BL, Snyder SH

Abstract

[3H]Nitrendipine binding to drug receptor sites associated with calcium channels is allosterically regulated by a diverse group of calcium channel antagonists. Verapamil, D-600 (methoxyverapamil), tiapamil, lidoflazine, flunarizine, cinnarizine, and prenylamine all reduce [3H]nitrendipine binding affinity. By contrast, diltiazem, a benzothiazepine calcium channel antagonist, enhances [3H]nitrendipine binding. All these drug effects involve a single site allosterically linked to the [3H]nitrendipine binding site. Inhibition of [3H]nitrendipine binding by prenylamine, lidoflazine, or tiapamil is reversed by D-600 and diltiazem, which alone respectively slightly reduce or enhance [3H]nitrendipine binding. Diltiazem reverses the inhibition of [3H]nitrendipine binding by D-600. Our prediction that drugs allosterically regulating [3H]nitrendipine binding should be calcium antagonists is confirmed by calcium antagonism in guinea pig ileum observed with the antihistamine dimethindene, the neuroleptics thioridazine and mesoridazine, and the anticholinergic biperiden.

MeSH Terms

Binding, Competitive Calcium Channel Blockers/classification,metabolism Ileum/metabolism Kinetics Nifedipine/analogs & derivatives,metabolism Nitrendipine

Chemicals

Calcium Channel Blockers Nitrendipine Nifedipine

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Murphy K M

Gould R J

Largent B L

Snyder S H

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20 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.80.3.860

Published

1983-02-00

Pages

860-4

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC393480

Subset

Grants

NIDA NIH HHS · DA-00266 · United States

NIMH NIH HHS · MH-18501 · United States

NINDS NIH HHS · NS-16375 · United States

External Links

PubMed source DOI: 10.1073/pnas.80.3.860 PMC Full Text View journal details

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A unitary mechanism of calcium antagonist drug action.

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