Asymmetric catecholimidazolines and catecholamidines

Affinity and efficacy relationships at the alpha adrenoreceptor in rat aorta

P. J. Rice, A. Hamada, Duane Miller, P. N. Patil

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11 Citations (Scopus)

Abstract

The epinephrine (EPI) stereoisomers interact with the alpha adrenoreceptor according to the Easson-Stedman model with an order of potency of (-)-EPI > (+)-EPI = Epinine. A series of catecholimidazolines (CI) and catecholamidines (CA) were compared with the EPI series for the relationship of stereoisomerism to potency, afffinity and efficacy. Within each group of desoxy compound and stereoisomers obtained by -OH substitution at the benzylic position, differences in potency were found to be due solely to differences in affinity; differences in efficacy were not significant. The stereoisomers of the CI and CA series followed the order of potency predicted by the Easson-Stedman model: (-)-isomer > (+)-isomer. The desoxy analogs, in contrast to the prediction based on the Easson-Stedman hypothesis, were equal (CI) or greater (CA) in potency than the more potent (-)-isomer of each series. Possible explanations for this include differences in physical properties in the desoxy analogs of CI and CA compared with the corresponding enantiomers. Methyl or benzyl substitution at C-4 of the imidazoline ring decreased potency over 100-fold; potency differences between enantiomers were negligible. Thus, the Easson-Stedman model cannot be extended to either the CI or CA series of alpha adrenoreceptor agonists.

Original languageEnglish (US)
Pages (from-to)121-130
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume242
Issue number1
StatePublished - 1987
Externally publishedYes

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Stereoisomerism
Epinephrine
Aorta
Deoxyepinephrine
Imidazolines

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Asymmetric catecholimidazolines and catecholamidines: Affinity and efficacy relationships at the alpha adrenoreceptor in rat aorta",
abstract = "The epinephrine (EPI) stereoisomers interact with the alpha adrenoreceptor according to the Easson-Stedman model with an order of potency of (-)-EPI > (+)-EPI = Epinine. A series of catecholimidazolines (CI) and catecholamidines (CA) were compared with the EPI series for the relationship of stereoisomerism to potency, afffinity and efficacy. Within each group of desoxy compound and stereoisomers obtained by -OH substitution at the benzylic position, differences in potency were found to be due solely to differences in affinity; differences in efficacy were not significant. The stereoisomers of the CI and CA series followed the order of potency predicted by the Easson-Stedman model: (-)-isomer > (+)-isomer. The desoxy analogs, in contrast to the prediction based on the Easson-Stedman hypothesis, were equal (CI) or greater (CA) in potency than the more potent (-)-isomer of each series. Possible explanations for this include differences in physical properties in the desoxy analogs of CI and CA compared with the corresponding enantiomers. Methyl or benzyl substitution at C-4 of the imidazoline ring decreased potency over 100-fold; potency differences between enantiomers were negligible. Thus, the Easson-Stedman model cannot be extended to either the CI or CA series of alpha adrenoreceptor agonists.",
author = "Rice, {P. J.} and A. Hamada and Duane Miller and Patil, {P. N.}",
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T1 - Asymmetric catecholimidazolines and catecholamidines

T2 - Affinity and efficacy relationships at the alpha adrenoreceptor in rat aorta

AU - Rice, P. J.

AU - Hamada, A.

AU - Miller, Duane

AU - Patil, P. N.

PY - 1987

Y1 - 1987

N2 - The epinephrine (EPI) stereoisomers interact with the alpha adrenoreceptor according to the Easson-Stedman model with an order of potency of (-)-EPI > (+)-EPI = Epinine. A series of catecholimidazolines (CI) and catecholamidines (CA) were compared with the EPI series for the relationship of stereoisomerism to potency, afffinity and efficacy. Within each group of desoxy compound and stereoisomers obtained by -OH substitution at the benzylic position, differences in potency were found to be due solely to differences in affinity; differences in efficacy were not significant. The stereoisomers of the CI and CA series followed the order of potency predicted by the Easson-Stedman model: (-)-isomer > (+)-isomer. The desoxy analogs, in contrast to the prediction based on the Easson-Stedman hypothesis, were equal (CI) or greater (CA) in potency than the more potent (-)-isomer of each series. Possible explanations for this include differences in physical properties in the desoxy analogs of CI and CA compared with the corresponding enantiomers. Methyl or benzyl substitution at C-4 of the imidazoline ring decreased potency over 100-fold; potency differences between enantiomers were negligible. Thus, the Easson-Stedman model cannot be extended to either the CI or CA series of alpha adrenoreceptor agonists.

AB - The epinephrine (EPI) stereoisomers interact with the alpha adrenoreceptor according to the Easson-Stedman model with an order of potency of (-)-EPI > (+)-EPI = Epinine. A series of catecholimidazolines (CI) and catecholamidines (CA) were compared with the EPI series for the relationship of stereoisomerism to potency, afffinity and efficacy. Within each group of desoxy compound and stereoisomers obtained by -OH substitution at the benzylic position, differences in potency were found to be due solely to differences in affinity; differences in efficacy were not significant. The stereoisomers of the CI and CA series followed the order of potency predicted by the Easson-Stedman model: (-)-isomer > (+)-isomer. The desoxy analogs, in contrast to the prediction based on the Easson-Stedman hypothesis, were equal (CI) or greater (CA) in potency than the more potent (-)-isomer of each series. Possible explanations for this include differences in physical properties in the desoxy analogs of CI and CA compared with the corresponding enantiomers. Methyl or benzyl substitution at C-4 of the imidazoline ring decreased potency over 100-fold; potency differences between enantiomers were negligible. Thus, the Easson-Stedman model cannot be extended to either the CI or CA series of alpha adrenoreceptor agonists.

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