Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Bertolino, F. et al.

Intrinsic activity of the non-prostanoid thromboxane A2 receptor antagonist, daltroban (BM 13,505), in human platelets in vitro and in the rat vasculature in vivo.

1. We evaluated the effects of daltroban on (i) human platelet shape change and aggregation in vitro, and (ii) mean systemic and pulmonary arterial pressures (MAP and MPAP, respectively) as well as haematocrit, in anaesthetized, open-chest Sprague-Dawley rats, compared with those of a chemically distinct prostanoid thromboxane A2 (TxA2) receptor antagonist, SQ 29,548, and agonist, U-46619. 2. In human platelets in vitro, daltroban (10 nM-100 microM; n = 6 per group) concentration-dependently induced shape change, attaining at 50 microM, a maximum amplitude of 0.83 +/- 0.09 mV representing 46.4 +/- 4.8% of that evoked by U-46619 (1.78 +/- 0.20 mV at 0.2 microM; n = 9); and inhibited U-46619-induced platelet aggregation with an IC50 of 77 (41-161)nM. SQ 29,548 (10 nM-100 microM; n = 6 per group) failed to evoke any platelet shape change, but potently inhibited U-46619-induced platelet aggregation with an IC50 < 10 nM. 3. In anaesthetized rats in vivo, daltroban (10-2500 micrograms kg-1, i.v. infused over 2 min; n = 4-8 per group) produced a bell-shaped dose-response curve for MPAP and haematocrit, and evoked maximal increases of 12.7 +/- 2.1 mmHg and 5.8 +/- 1.5% at 80 micrograms kg-1 (n = 6) and 630 micrograms kg-1 (n = 8), respectively (both P < 0.05) with ED50s of 20 (16-29) and 217 (129-331) micrograms kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

References

Intrinsic activity of the non-prostanoid thromboxane A2 receptor antagonist, daltroban (BM 13,505), in human platelets in vitro and in the rat vasculature in vivo. Bertolino, F., Valentin, J.P., Maffre, M., Grelac, F., Bessac, A.M., Maclouf, J., Delhon, A., Lévy-Toledano, S., Patoiseau, J.F., Colpaert, F.C. Br. J. Pharmacol. (1995) [Pubmed]

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