Kinetics of accumulation, efflux and the pharmacological effects of tritiated dihydroazapetine on the rabbit aorta

R. R. Ruffolo, J. W. Fowble, Duane Miller, P. N. Patil

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Azapetine, a potent alpha adrenergic antagonist, was catalytically reduced with tritium and hydrogen gas to form dihydroazapetine. The pA2 of azapetine was 7.9 whereas that of dihydroazapetine was 6.6, corresponding to a 20 fold decrease in potency. 3H dihydroazapetine is accumulated into 3 kinetically distinct compartments in the denervated rabbit aorta. Likewise, efflux of the labeled antagonist occurs from 3 compartments. The rate constant for onset of alpha adrenoreceptor blockade is 3.15 min-1 which is nearly identical to the rate constant for entry of 3H dihydroazapetine into a rapidly filling compartment (3.86 min-1) possibly representing the extracellular space. These data are consistent with the hypothesis that onset of alpha adrenoreceptor blockade by dihydroazapetine is diffusion limited.

Original languageEnglish (US)
Pages (from-to)278-286
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume202
Issue number2
StatePublished - 1977
Externally publishedYes

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Aorta
Pharmacology
Rabbits
Adrenergic alpha-Antagonists
Tritium
Extracellular Space
Hydrogen
Gases
dihydroazapetine
azapetine

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Kinetics of accumulation, efflux and the pharmacological effects of tritiated dihydroazapetine on the rabbit aorta. / Ruffolo, R. R.; Fowble, J. W.; Miller, Duane; Patil, P. N.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 202, No. 2, 1977, p. 278-286.

Research output: Contribution to journalArticle

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