Daltroban
(Synonyms: 达尔卓潘,BM-13505; SKF 96148) 目录号 : GC38763
A TP antagonist
Cas No.:79094-20-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Daltroban is a thromboxane receptor (TP) antagonist.1 It inhibits aggregation of isolated human platelets induced by the TP agonist U-46619 . Daltroban increases mean pulmonary arterial pressure (MPAP), mean arterial pressure (MAP), and hematocrit levels in anesthetized rats (ED50s = 20, 217, and 94 ?g/kg, respectively). It maintains post-reinfusion MAP and superior mesenteric artery flow in a cat model of hemorrhagic shock when administered at a dose of 1 mg/kg.2 Daltroban (0.25-2 mg/kg) increases survival and decreases circulating platelet count in a rabbit model of sodium arachidonate-induced sudden death.3
1.Bertolino, F., Valentin, J.P., Maffre, M., 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 vivoBr. J. Pharmacol.115210-216(1995) 2.Bitterman, H., Yanagisawa, A., and Lefer, A.M.Beneficial actions of thromboxane receptor antagonism in hemorrhagic shockCirc. Shock20(1)1-11(1986) 3.Lefer, D.J., Mentley, R.K., and Lefer, A.M.Protective effects of a new specific thromboxane antagonist in arachidonate-induced sudden deathArch. Int. Pharmacodyn. Ther.287(1)89-95(1987)
| Cas No. | 79094-20-5 | SDF | |
| 别名 | 达尔卓潘,BM-13505; SKF 96148 | ||
| Canonical SMILES | O=C(CC1=CC=C(C=C1)CCNS(=O)(C2=CC=C(C=C2)Cl)=O)O | ||
| 分子式 | C16H16ClNO4S | 分子量 | 353.82 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 1 mM | 2.8263 mL | 14.1315 mL | 28.263 mL |
| 5 mM | 0.5653 mL | 2.8263 mL | 5.6526 mL |
| 10 mM | 0.2826 mL | 1.4131 mL | 2.8263 mL |
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Evidence for partial agonist properties of Daltroban (BM 13,505) at TP receptors in the anaesthetized open-chest rat
Naunyn Schmiedebergs Arch Pharmacol 1997 Oct;356(4):462-6.PMID:9349632DOI:10.1007/pl00005077.
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-anesthetized, 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) microg/kg i.v.. Daltroban increased MPAP in a bell-shaped manner, with an apparent ED50 [29 (21-35) microg/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 microg/kg) or Daltroban (80 microg/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 microg/kg) antagonized, although not fully, U-46619 (20 microg/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 microg/kg), Daltroban (80 microg/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.
Daltroban, a thromboxane receptor antagonist, protects the myocardium against reperfusion injury following myocardial ischemia without protecting the coronary endothelium
Methods Find Exp Clin Pharmacol 1990 Dec;12(10):651-6.PMID:1966110doi
The effects of Daltroban, a specific thromboxane receptor antagonist, were investigated in a model of myocardial ischemia consisting of 1.5 h of coronary artery occlusion followed by reperfusion for 4.5 h in anesthetized cats. Daltroban (1 mg/kg) was infused as a bolus 10 min prior to reperfusion of the left anterior descending (LAD) coronary artery. Daltroban infusion resulted in a significantly lower necrotic area expressed as a percentage of the myocardial area-at-risk compared to the MI + vehicle group. However, Daltroban failed to retard increases in myeloperoxidase activity in the ischemic myocardium, indicating no reduction in neutrophil accumulation. Moreover, left anterior descending coronary artery ring preparations isolated from Daltroban treated MI cats exhibited endothelial dysfunction following ischemia reperfusion. Thus, Daltroban significantly protected the myocardium from reperfusion injury without protecting the coronary endothelium or retarding neutrophil accumulation.
Daltroban blocks thromboxane responses in the pulmonary vascular bed of the cat
J Appl Physiol (1985) 1992 Jun;72(6):2305-10.PMID:1385804DOI:10.1152/jappl.1992.72.6.2305.
The influence of Daltroban (BM13.505; SK&F 96148), a thromboxane (Tx) A2-receptor-blocking agent, on responses to the TxA2 mimics U-46619 and U-44069 was investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. Daltroban (5 mg/kg iv) had no significant effect on mean baseline vascular pressures but significantly decreased responses to the TxA2 mimics without altering responses to prostaglandin (PG) F2 alpha or PGD2 or the PGD2 metabolite 9 alpha, 11 beta-PGF2. Dose-response curves for U-46619 and U-44069 were shifted to the right in a parallel manner, and Daltroban had no significant effect on responses to norepinephrine, serotonin, angiotensin II, BAY K 8644, endothelin-(ET) 1, ET-2, or platelet-activating factor (PAF). After administration of Daltroban, responses to U-46619 returned to 50% of control in 90 min and responses to the PG and TxA2 precursor arachidonic acid were decreased significantly. These results suggest that Daltroban selectively antagonizes TxA2-receptor-mediated responses in a competitive and reversible manner. These data provide support for the hypothesis that discrete TxA2 receptors unrelated to receptors stimulated by PGF2 alpha, PGD2, or 9 alpha, 11 beta-PGF2 are present in the pulmonary vascular bed of the cat. The present data suggest that pulmonary vasoconstrictor responses to PAF and ET peptides are not dependent on activation of TxA2 receptors in the cat.
Atherosclerosis in the aorta of hypercholesterolemic rabbits and the influence of Daltroban
Exp Pathol 1991;41(2):57-69.PMID:1828033DOI:10.1016/s0232-1513(11)80001-0.
These studies have examined aortic atherogenesis in cholesterol-fed rabbits and have correlated the effects of Daltroban to the pathomechanism of the vessel wall lesions. After feeding a 0.5% cholesterol-enriched diet for 96 d atherosclerotic alterations were seen, which exhibited a proximo-distal pattern, to which the branching of the aorta contributed considerably. Depending on their localization and size a varying cellular constitution of the plaques was obvious. Large plaques, which were mainly seen in the aortic arch and the proximal descending thoracic aorta, consisted of numerous proliferating cells, masses of fibrillar ground substance, clusters of foam cells, and rarely contained cholesterol crystals and necroses. Emerging plaques mainly found in distal thoracic and abdominal aorta imposed as fatty streaks. Daltroban treatment, used in a clinically relevant doses of 10 mg/kg b. wt. per day, reduced extension and protrusional area of plaques to about 40%, which was evaluated using a newly developed computerized morphormetric method, in association with significant reductions in free cholesterol content within the aorta. The results suggest that Daltroban inhibits the progression of atherosclerosis in cholesterol-fed rabbits. This effect may be related to its antagonistic interaction with the thromboxane A2 receptor and also to an inhibition of the cholesterol metabolism.
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
Br J Pharmacol 1995 May;115(1):210-6.PMID:7647979DOI:10.1111/j.1476-5381.1995.tb16341.x.
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. By comparison, U-46619(0.16-20 microg kg-1, i.v.), induced dose-dependent increases in MPAP and haematocrit (25.4 +/- 1.0 mmHg and 16.1 +/- 2.9% at the highest dose; n = 12, both P<0.01), with ED50s of 1.8 (1.3-2.5) and 3.9(3.5- 5.4) microg kg- 1, respectively. Daltroban dose-dependently increased MAP with a maximum amplitude of 42.2 +/- 4.4 mmHg at a dose of 80 microg kg-1 [ED50 = 94 (64-125) microg kg-1], similar to that induced by U-46619 (41.3 +/- 9.6 mmHg) at a dose of 0.63 microg kg-1 [ED50= 0.22 (0.13-0.24) microg kg-1]. SQ 29,548(10-2500 microg kg-1, i.v.; n =4 per group) failed to modify significantly any of these parameters.4. Our results clearly demonstrate that Daltroban, in a similar manner to the TxA2 analogue, U-46619,but unlike the TxA2 receptor antagonist, SQ 29,548, exhibits significant intrinsic activity in human platelets in vitro and in the rat vasculature in vivo, possibly through TxA2 receptor activation.