Lactamimides: A novel chemical class of calcium antagonists with diltiazem-like properties

Michael G. Palfreyman, Mark W. Dudley, Hsien C. Cheng, Anis K. Mir, Shizuo Yamada, William R. Roeske, Takaaki Obata, Henry I. Yamamura

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Abstract

The effects of a series of lactamimides on [3H]d-cis-diltiazem binding to rat brain membranes, on [3H]nitrendipine binding to cardiac membranes, and on calcium-induced contractions in depolarized guinea pig taenia and ileum preparations were examined. Several of the lactamimides examined displaced [3H]d-cis-diltiazem binding and antagonized, in a competitive fashion, calcium-induced contractions. Over the series of lactamimides, there was a highly significant, positive linear correlation (r = 0.87, P < 0.001) between their potency to displace [3H]d-cis-diltiazem and their potency to antagonize calcium-induced contractions in the depolarized taenia and ileum preparations. Of the lactamimides examined, MDL 16,582A [N-(2,2-diphenylpentyl)azacyclotridecan-2-imine · hydrochloride] had potency equivalent to d-cis-diltiazem with pA2 values of 7.27 and 7.38, respectively, against calcium-induced contractions in the guinea pig ileum. These lactamimides are a novel chemical class displaying diltiazem-like calcium antagonist properties.

Original languageEnglish (US)
Pages (from-to)2459-2465
Number of pages7
JournalBiochemical Pharmacology
Volume38
Issue number15
DOIs
StatePublished - Aug 1 1989

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ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Palfreyman, M. G., Dudley, M. W., Cheng, H. C., Mir, A. K., Yamada, S., Roeske, W. R., Obata, T., & Yamamura, H. I. (1989). Lactamimides: A novel chemical class of calcium antagonists with diltiazem-like properties. Biochemical Pharmacology, 38(15), 2459-2465. https://doi.org/10.1016/0006-2952(89)90089-0