Erythrocyte adenosine transport a rapid screening test for cardiovascular drugs

Pollen K.F. Yeung, Susan J. Mosher, Rongshi Li, Patrick S. Farmer, Gerald A. Klassen, P. Timothy Pollak, Mark McMullen, Greg Ferrrier

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Abstract

An erythrocyte (RBC) model based on whole blood was used to investigate the effect of cardiovascular drugs on the uptake of adenosine in vitro. Fresh whole blood obtained from healthy volunteers was allowed to equilibrate with various concentrations (5-1000 μM) of a tested agent. (2-3H)-Adenosine was used as a substrate, and the reaction was terminated after 2 sec of incubation at room temperature by rapid addition of a "Stopping Solution" which was a mixture of erythro-9-(2-hydroxy-3-nonyl)adenine, dipyridamole, and EDTA. The mixture was centrifuged (1760 g, 4°C, 10 min), and the radioactivity of an aliquot of the supernatant was determined by a scintillation counter. The results showed that dipyridamole was the most potent agent tested (IC50 = 0.2 μM). Amongst the calcium antagonists studied, isradipine was most potent, followed by verapamil, clentiazem, diltiazem, and then nifedipine. The racemates of two metabolites of diltiazem, Mx and Mb, were more potent than the parent drug. The antiarrhythmic agents, amiodarone and sotalol, the two new lipid peroxidation inhibitors, U-74389F and U-78517F, and the anxiolytic agent, alprazolam, were as active as verapamil. The ß-receptor antagonist propranolol and the angiotensin converting enzyme (ACE) inhibitor, enalapril, were practically inactive. In addition, the model was stereoselective such that the S(-)-enantiomer of verapamil was considerably more potent than the R(+)-antipote, whereas d(+)-sotalol was practically inactive compared to racemic sotalol.

Original languageEnglish (US)
Pages (from-to)163-167
Number of pages5
JournalJournal of Pharmacological and Toxicological Methods
Volume30
Issue number3
DOIs
Publication statusPublished - Nov 1993

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Keywords

  • Adenosine transporter
  • Cardiovascular drugs
  • Screening test

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Yeung, P. K. F., Mosher, S. J., Li, R., Farmer, P. S., Klassen, G. A., Pollak, P. T., ... Ferrrier, G. (1993). Erythrocyte adenosine transport a rapid screening test for cardiovascular drugs. Journal of Pharmacological and Toxicological Methods, 30(3), 163-167. https://doi.org/10.1016/1056-8719(93)90041-C