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1. The aim of the present study was to determine the effect of the nucleoside transporter inhibitor, draflazine, on the force of contraction in human myocardium and the affinity of the compound for the nucleoside transporter. Nucleoside transport inhibitors, like draflazine, are of potential importance for cardiopreservation of donor hearts for heart transplantation. 2. Functional experiments were performed in isolated electrically driven (1 Hz, 1.8 mmol l-1 Ca2+) human atrial trabeculae and ventricular papillary muscle strips. The affinity of draflazine for the myocardial nucleoside transporter was studied in isolated membranes from human ventricular myocardium and human erythrocytes in radioligand binding experiments using [3H]-nitrobenzylthioinosine ([3H]-NBTI). Dipyridamole was studied for comparison. 3. In membranes from human myocardium and erythrocytes, [3H]-NTBI labelled 1.18 pmol mg-1 protein and 23.0 pmol mg-1 protein, respectively, nucleoside transporter molecules with a KD value of 0.8 nmol l-1. Draflazine concentration-dependently inhibited binding of [3H]-NBTI to myocardial and erythrocyte membranes with a K(i)-value of 4.5 nmol l-1. The potency as judged from the K(i) values was ten times greater than that of dipyridamole in both myocardial and erythrocyte membranes. 4. Draflazine, at concentrations up to 100 mumol l-1, did not produce negative inotropic effects in atrial and ventricular myocardium. (-)-N6-phenylisopropyladenosine (R-PIA) and carbachol did not reduce force of contraction in ventricular myocardium, but exerted concentration-dependent direct negative inotropic effects in atrial myocardium. 5. The data provide evidence that draflazine specifically binds to the nucleoside transporter of the human heart and erythrocytes with high affinity. The compound does not produce negative inotropic effects at concentrations as high as 100 micromol 1-1.6. Draflazine could be a useful agent for cardio preservation because it does not produce cardio depressant effects. Thus, it may be possible to perfuse explanted hearts directly with this agent without the hazard of cardiodepression.
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
February 2020,
Biochemical pharmacology,
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
March 1985,
The Journal of biological chemistry,
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
January 1996,
European journal of clinical pharmacology,
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
April 2000,
Naunyn-Schmiedeberg's archives of pharmacology,
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
November 1996,
British journal of clinical pharmacology,
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
July 2008,
Xenobiotica; the fate of foreign compounds in biological systems,
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
July 1998,
The Journal of pharmacology and experimental therapeutics,
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
January 1994,
European journal of pharmacology,
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
December 2015,
Biochemical pharmacology,
M Böhm, and
C Weinhold, and
R H Schwinger, and
J Müller-Ehmsen, and
D Böhm, and
H Reichenspurner, and
B Reichart, and
E Erdmann
June 1993,
British journal of pharmacology,
