Evidence for partial agonist properties of daltroban (BM 13,505) at TP receptors in the anaesthetized open-chest rat

Frédéric Bertolino, Jean Pierre Valentin, Jean François Patoiseau, Jean Pierre Rieu, Francis C. Colpaert, Gareth W. John

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


We sought to determine whether the intrinsic pulmonary hypertensive activity of the purported thromboxane A2/prostanoid (TP) receptor antagonist, daltroban, was mediated by TP receptors, using the high efficacy TP receptor agonist, U-46619, and the silent TP receptor antagonist, SQ 29,548. In pentobarbitone-anaesthetized, open-chest rats (n = 4-10 per group), non-cumulative injections of U-46619, dose-dependently increased mean pulmonary arterial pressure (MPAP) with an ED50 (geometric mean with 95% confidence limits in parentheses) of 1.4 (1.1-2.3) μg/kg i.v.. Daltroban increased MPAP in a bell-shaped manner, with an apparent ED50 129 (21-35)μg/kg i.v.] being 21 fold less potent than that of U-46619. The maximal pulmonary hypertensive responses evoked by daltroban represented about half those induced by U-46619 (25.4 ± 1.0 vs. 12.7 ± 2 mmHg; P < 0.05 between groups). The TP receptor antagonist SQ 29,548 fully antagonized increases in MPAP evoked by equihypertensive doses of U-46619 (1.25 μg/kg) or daltroban (80 μg/kg). Further experiments were carried out to determine whether daltroban antagonized the pulmonary hypertensive responses evoked by the high efficacy agonist, U-46619, or by itself as receptor theory would predict for a partial agonist. Daltroban (10-2500 μg/kg) antagonized, although not fully, U-46619 (20 μg/kg)-evoked pulmonary hypertensive responses, since prominent intrinsic pulmonary hypertensive effects of daltroban were observed in the same range of doses. Furthermore, in contrast to U-46619 (1.25 μg/kg), daltroban (80 μg/kg) failed to evoke a second pulmonary hypertensive response following a previous injection, as would be expected for a partial agonist. Collectively, the results strongly suggest that daltroban behaves as a partial agonist at TP receptors in the pulmonary vascular bed of the rat in vivo.

Original languageEnglish
Pages (from-to)462-466
Number of pages5
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Issue number4
StatePublished - 1997
Externally publishedYes


  • Daltroban
  • Partial agonist
  • Pulmonary hypertension
  • TP receptors


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