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Chemical Compound Review

Draflazina     1-[(4-amino-2,6-dichloro...

Synonyms: Draflazine, Draflazinum, SureCN215826, CHEMBL1628717, KB-216952, ...
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Disease relevance of R 75231


High impact information on R 75231

  • After the intravenous draflazine infusion, these values were 1.6 +/- 0.2 ml/100 ml forearm per min for placebo and 2.1 +/- 0.3, 3.3 +/- 0.6, 5.8 +/- 1.1, 6.9 +/- 1.4, 14.4 +/- 2.9, and 23.5 +/- 4.0 ml/100 ml forearm per min, respectively (Friedman ANOVA: P < 0.05 before vs after draflazine infusion) [5].
  • Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P<.001 for both) and in the zero-flow protocol (76+/-3% versus 59+/-4% [saline] and 46+/-9% [8SPT], P<.05 for both) [1].
  • In a dose-finding study on draflazine infusions into the brachial artery (n=10), we identified an optimal dose of 250 ng/min per deciliter of forearm tissue that induced considerable local nucleoside transport inhibition (approximately 40%) without systemic effects [6].
  • In the main study, we investigated the effects of this draflazine dose on sympathetic-mediated norepinephrine spillover during lower body negative pressure (-25 mm Hg) by the use of the [3H]norepinephrine isotope dilution technique (n=25) [6].
  • The ENT1 transporters exhibit distinctive species differences in their sensitivities to inhibition by dipyridamole, dilazep and draflazine (human>mouse>rat) [7].

Chemical compound and disease context of R 75231


Biological context of R 75231

  • However, increased endogenous levels by draflazine enhance downregulation of function and reduce signs of anaerobic metabolism [9].
  • However, draflazine enhanced the reduction in heart rate, contractile force and MVO(2), with less release of H+ and CO2 [9].
  • 3. The pharmacokinetics of draflazine in blood were determined in each subject and characterized by a two-compartment pharmacokinetic model [10].
  • We conclude that nucleoside transport inhibition with draflazine does not alter global and hepatosplanchnic hemodynamics but may decrease gut mucosal perfusion and renal blood flow [8].
  • Dose-response curves indicated that the IC50 values of draflazine and R88016 were approximately 0.5 microM and 10 microM, respectively [11].

Anatomical context of R 75231

  • 5. The data provide evidence that draflazine specifically binds to the nucleoside transporter of the human heart and erythrocytes with high affinity.(ABSTRACT TRUNCATED AT 250 WORDS)[12]
  • Studies of the nucleoside transporter inhibitor, draflazine, in the human myocardium [12].
  • In the control group, only three fetuses recovered and survived, whereas in the R-75231 group, all seven animals recovered after severe asphyxia [4].
  • Draflazine concentration-dependently inhibited binding of [3H]-NBTI to myocardial and erythrocyte membranes with a K(i)-value of 4.5 nmol l-1 [12].
  • On the basis of these findings it is suggested that a 15 min infusion of 1 mg draflazine followed by an infusion of 1 mg h-1 could be appropriate in patients undergoing a coronary artery bypass grafting [13].

Associations of R 75231 with other chemical compounds


Gene context of R 75231

  • Draflazine and a series of 15 chemically related compounds were compared for their abilities to: (a) inhibit the binding of [3H]NBMPR to the es/ENT1 transporter in mouse Ehrlich cell and human erythrocyte membranes, and (b) inhibit the es/ENT1 and ei/ENT2 transporter-mediated uptake of [3H]uridine in Ehrlich cells [15].
  • Thus, the cardioprotective effects of R 75231 are not mediated by adenosine A1 receptor activation and, thus, probably are not caused by its activity as a nucleoside transport inhibitor [3].
  • At end of LFI mRNA-level of PLB was higher in draflazine-treated hearts compared to both other groups (P<0.01 vs both) [9].
  • In the R 75231 group, renin, angiotension I, and angiotensin II levels were significantly lower [16].

Analytical, diagnostic and therapeutic context of R 75231

  • Intravenous injection of 0.5 mg draflazine did not affect any of the measured hemodynamic parameters but still induced a significant ex vivo nucleoside-transport inhibition of 31.5 +/- 4.1% (P < 0.05 vs placebo) [5].
  • Draflazine did not affect forearm blood flow (venous occlusion plethysmography) [5].
  • The percentage increase in myocardial blood flow during asphyxia, measured with radioactive microspheres, was significantly higher in the R-75231-treated group compared with the control group (437 and 284%, respectively) [4].
  • R 75231 caused only modest improvements in reperfusion contractile function, whereas it profoundly reduced LDH release [3].
  • Nucleoside transport inhibitors, like draflazine, are of potential importance for cardiopreservation of donor hearts for heart transplantation [12].


  1. Importance of endogenous adenosine during ischemia and reperfusion in neonatal porcine hearts. Sommerschild, H.T., Grund, F., Offstad, J., Jynge, P., Ilebekk, A., Kirkebøen, K.A. Circulation (1997) [Pubmed]
  2. Novel approach for enhancing atrioventricular nodal conduction delay mediated by endogenous adenosine. Kollias-Baker, C., Xu, J., Pelleg, A., Belardinelli, L. Circ. Res. (1994) [Pubmed]
  3. The cardioprotective effects of R 75231 and lidoflazine are not caused by adenosine A1 receptor activation. Grover, G.J., Sleph, P.G. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  4. The effect of adenosine transport inhibition on cardiovascular function and survival after severe asphyxia in fetal lambs. de Haan, H.H., de Haan, J., Van Reempts, J.L., Van Belle, H., Hasaart, T.H. Pediatr. Res. (1993) [Pubmed]
  5. Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection. Rongen, G.A., Smits, P., Ver Donck, K., Willemsen, J.J., De Abreu, R.A., Van Belle, H., Thien, T. J. Clin. Invest. (1995) [Pubmed]
  6. Presynaptic inhibition of norepinephrine release from sympathetic nerve endings by endogenous adenosine. Rongen, G.A., Lenders, J.W., Lambrou, J., Willemsen, J.J., Van Belle, H., Thien, T., Smits, P. Hypertension (1996) [Pubmed]
  7. Molecular cloning and functional characterization of inhibitor-sensitive (mENT1) and inhibitor-resistant (mENT2) equilibrative nucleoside transporters from mouse brain. Kiss, A., Farah, K., Kim, J., Garriock, R.J., Drysdale, T.A., Hammond, J.R. Biochem. J. (2000) [Pubmed]
  8. Effects of nucleoside transport inhibition on hepatosplanchnic perfusion, oxygen extraction capabilities, and TNF release during acute endotoxic shock. Zhang, H., De Jongh, R., Cherkaoui, S., Shahram, M., Vray, B., Vincent, J.L. Shock (2001) [Pubmed]
  9. Elevated levels of endogenous adenosine alter metabolism and enhance reduction in contractile function during low-flow ischemia: associated changes in expression of Ca(2+)-ATPase and phospholamban. Sommerschild, H.T., Lunde, P.K., Deindl, E., Jynge, P., Ilebekk, A., Kirkebøen, K.A. J. Mol. Cell. Cardiol. (1999) [Pubmed]
  10. The implications of non-linear red blood cell partitioning for the pharmacokinetics and pharmacodynamics of the nucleoside transport inhibitor draflazine. Snoeck, E., Jacqmin, P., Van Peer, A., Danhof, M., Ver Donck, K., Van Belle, H., Woestenborghs, R., Crabbé, R., Van Gool, R., Dupont, A., Heykants, J. British journal of clinical pharmacology. (1996) [Pubmed]
  11. Nucleoside transport inhibition and platelet aggregation in human blood: R75231 and its enantiomers, draflazine and R88016. Beukers, M.W., Kerkhof, C.J., IJzerman, A.P., Soudijn, W. Eur. J. Pharmacol. (1994) [Pubmed]
  12. Studies of the nucleoside transporter inhibitor, draflazine, in the human myocardium. Böhm, M., Weinhold, C., Schwinger, R.H., Müller-Ehmsen, J., Böhm, D., Reichenspurner, H., Reichart, B., Erdmann, E. Br. J. Pharmacol. (1994) [Pubmed]
  13. Population analysis of the non linear red blood cell partitioning and the concentration-effect relationship of draflazine following various infusion rates. Snoeck, E., Piotrovskij, V., Jacqmin, P., Van Peer, A., Danhof, M., Ver Donck, K., Woestenborghs, R., Van Belle, H., Van Bortel, L., Van Gool, R., Dupont, A.G., Heykants, J. British journal of clinical pharmacology. (1997) [Pubmed]
  14. Physiological red blood cell kinetic model to explain the apparent discrepancy between adenosine breakdown inhibition and nucleoside transporter occupancy of draflazine. Snoeck, E., Ver Donck, K., Jacqmin, P., Van Belle, H., Dupont, A.G., Van Peer, A., Danhof, M. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  15. Interaction of a series of draflazine analogues with equilibrative nucleoside transporters: species differences and transporter subtype selectivity. Hammond, J.R. Naunyn Schmiedebergs Arch. Pharmacol. (2000) [Pubmed]
  16. Protection of canine renal grafts by renin-angiotensin inhibition through nucleoside transport blockade. Booster, M.H., Yin, M., Maessen, J.G., Stubenitsky, B.M., Wijnen, R.M., Kootstra, G. Transpl. Int. (1995) [Pubmed]
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