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Research ArticleArticle

STERIC ASPECTS OF ADRENERGIC DRUGS. XI. INTERACTIONS OF DIBENAMINE AND BETA ADRENERGIC BLOCKERS

P. N. PATIL, A. TYE, C. MAY, S. HETEY and S. MIYAGI
Journal of Pharmacology and Experimental Therapeutics October 1968, 163 (2) 309-319;
P. N. PATIL
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A. TYE
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C. MAY
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S. HETEY
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S. MIYAGI
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Abstract

The ability of several beta adrenergic blockers and their optical isomers to protect the effects of norepinephrine from Dibenamine blockade was investigated in isolated rat vas deferens. In concentrations of from 3 x 10-6 M to 10-3 M, all beta adrenergic blockers protected the effects of norepinephrine from block by Dibenamine. If a 10-7 M concentration of phentolamine, which protected approximately 50% of the norepinephrine effect, is given a value of 1, the relative protective abilities of beta adrenergic blockers against Dibenamine blockade are as follows: (-)-H56/28 (1/30th) > (+)-H56/28 (1/100th) > (±)-pronethalol (1/300th) > l(+)-pronethalol (1/300th) > (±)-propranolol (1/1000th) > d(-)- INPEA (1/1000th) > l(+)-INPEA (1/3000th) = (±)-KO 592 (1/3000th) > (±)-IMA (1/3000th) > (±)-MJ 1999 (1/4000th). Similar protection of norepinephrine effects was also observed in catecholamine-depleted tissue. In another series of experiments, dose-response curves for norepinephrine were obtained in the presence of the same concentrations of beta adrenergic blockers as those used in the receptor protection experiments. In this series, all agents except isomers of H56/28 potentiated norepinephrine effects. Our conclusions are that all beta adrenergic blockers compete in varying degrees for both alpha adrenergic receptor and transfer sites. This property appears unrelated to their beta adrenergic blocking effect, for 1) the optical isomers showed little or no difference, and 2) only (-)-isomers are potent beta adrenergic blockers. Thus, it may be that mainly two-point interaction, not involving the hydroxy group on the beta carbon, would account for the alpha adrenergic receptor-protecting ability of beta adrenergic blockers.

Footnotes

    • Received March 14, 1968.
    • Accepted June 17, 1968.
  • © 1968 by the Williams & Wilkins Co.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 163, Issue 2
1 Oct 1968
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Research ArticleArticle

STERIC ASPECTS OF ADRENERGIC DRUGS. XI. INTERACTIONS OF DIBENAMINE AND BETA ADRENERGIC BLOCKERS

P. N. PATIL, A. TYE, C. MAY, S. HETEY and S. MIYAGI
Journal of Pharmacology and Experimental Therapeutics October 1, 1968, 163 (2) 309-319;

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Research ArticleArticle

STERIC ASPECTS OF ADRENERGIC DRUGS. XI. INTERACTIONS OF DIBENAMINE AND BETA ADRENERGIC BLOCKERS

P. N. PATIL, A. TYE, C. MAY, S. HETEY and S. MIYAGI
Journal of Pharmacology and Experimental Therapeutics October 1, 1968, 163 (2) 309-319;
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