Diltiazem: Lack of myocardial β-adrenergic receptor-binding capacity

S. F. Flaim, K. E. Flaim, Robert Zelis

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

It has been suggested that the mechanism of action of the calcium blocker diltiazem (DZ) is via β-receptor blockade. In order to test this hypothesis, the effects of DZ on the competitive binding of 3 H-dihydroalprenolol ( 3 H-DHA) to myocardial β-receptors were evaluated and compared to those of a known β-receptor agonist. Preliminary validation studies indicate that binding sites for 3 H-DHA exhibit stereospecificity for isoproterenol (IP) (l-IP>d-IP) and show greater affinity for l-epinephrine compared to l-norepinephrine. In order to test the binding capacity of DZ to β-adrenergic receptors, binding-concentration relationships were constructed for 3 H-DHA (3-60 nM) in the presence of no drugs, l-IP (10 -4 M), or DZ (2.2 x 10 -6 M). 3 H-DHA binding was significantly inhibited over the entire concentration range by l-IP but was unaffected by the other conditions. This study was repeated using 2 different concentrations of DZ (2.2 x 10 -5 and 2.2 x 10 -7 M) with a similar lack of inhibition of 3 H-DHA binding. These data indicate that DZ does not bind to myocardial β-receptors and, therefore, does not appear to act via a β-receptor-blocking activity.

Original languageEnglish (US)
Pages (from-to)306-312
Number of pages7
JournalPharmacology
Volume21
Issue number4
DOIs
StatePublished - Jan 1 1980

Fingerprint

Dihydroalprenolol
Diltiazem
Adrenergic Receptors
Isoproterenol
Competitive Binding
Validation Studies
Epinephrine
Norepinephrine
Binding Sites
Calcium
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Flaim, S. F. ; Flaim, K. E. ; Zelis, Robert. / Diltiazem : Lack of myocardial β-adrenergic receptor-binding capacity. In: Pharmacology. 1980 ; Vol. 21, No. 4. pp. 306-312.
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Diltiazem : Lack of myocardial β-adrenergic receptor-binding capacity. / Flaim, S. F.; Flaim, K. E.; Zelis, Robert.

In: Pharmacology, Vol. 21, No. 4, 01.01.1980, p. 306-312.

Research output: Contribution to journalArticle

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T2 - Lack of myocardial β-adrenergic receptor-binding capacity

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