Thromboxane A2 synthetase [1]

Ozagrel prevents oleic acid (OA) induced thromboxane A(2) generation and subsequently increased total protein concentration and the numbers of macrophages and neutrophils in bronchoalveolar lavage fluid and increased monocyte chemoattractant protein-1 andinterleukin-8 mRNA expression in the whole lung of guinea pigs. Ozagrel (3 mg/kg) decreases both the area and volume of the cortical infarction after ischemia-reperfusion of the middle cerebral artery in rat. Ozagrel also has suppressive effects on the neurologic deficits in the microthrombosis rat model. Ozagrel improves the reduced spontaneously locomotor activity and the obstruction of motor coordination in the conscious cerebral ischemia-reperfusion mouse model. Ozagrel suppresses the decrease in specific gravity of the brain tissue induced by the occlusion-reperfusion in the conscious cerebral ischemia-reperfusion SHR model, and recovers the postischemic decrease in cortical PO(2) after middle cerebral artery occlusion-reperfusion in cats. Ozagrel also increases the level of 6-keto-PGF(1alpha), a metabolite of prostaglandin I(2) (PGI(2)), in the brain tissue after cerebral ischemia-reperfusion, and the administration of PGI(2) improves the reduced spontaneous locomotor activity in the conscious cerebral ischemia-reperfusion mouse model. Ozagrel administered intravenously 30 min before oleic acid injection prevents the decrease in Pao(2) and pulmonary vascular hyper-permeability in guinea-pigs. Ozagrel also prevents increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB(2) and its weight ratio to 6-keto prostaglandin F(1alpha) in bronchoalveolar lavage fluid in guinea-pigs.

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In a conscious mouse cerebral ischemia-reperfusion model (bilateral common carotid artery occlusion), ozagrel (1-10 mg/kg i.v.) significantly prevented the decrease in spontaneous locomotor activity (cumulative wheel revolutions increased at 10-180 min post-reperfusion) compared to control. The effect at 10 mg/kg was similar to 3 mg/kg, suggesting lack of dose dependency possibly due to transient hypotensive effect at high doses. [1]
In the same mouse model with 30 min occlusion, ozagrel (0.3-10 mg/kg i.v.) reduced the motor coordination obstruction (falling score on rotarod) at 1-30 min post-reperfusion, with significant improvement at 0.3-3 mg/kg. Nizofenone also improved motor coordination but not spontaneous locomotor activity. [1]
In SHR rats subjected to two cycles of 30 min bilateral common carotid artery occlusion separated by 30 min reperfusion, ozagrel (1-10 mg/kg s.c. before each occlusion) lessened the decrease in cerebral cortical specific gravity (indicating reduced brain edema) measured 30 min after the second reperfusion. Nizofenone showed no effect. [1]
In cats with middle cerebral artery occlusion-reperfusion (2 h occlusion followed by reperfusion), ozagrel treatment restored cortical PO2 to pre-occlusion level by 60 min after reperfusion, whereas control group showed sustained decrease. Nizofenone increased PO2 above pre-occlusion level. [1]
In the mouse ischemia-reperfusion model, ozagrel (10 mg/kg) significantly blocked the increase in brain TXB2 (TXA2 metabolite) at 10 min after reperfusion and restored the decreased 6-keto-PGF1α (PGI2 metabolite) level. [1]
Exogenous PGI2 dose-dependently prevented the reduction in spontaneous locomotor activity after occlusion-reperfusion in mice, suggesting that increased PGI2 contributes to the beneficial effect of ozagrel. [1]

TXA2 and PGI2 levels in brain tissue were determined by radioimmunoassay. After drug administration, bilateral common carotid arteries were occluded for 10 min in conscious mice. Ten minutes after start of reperfusion, animals were decapitated, brains removed and frozen in liquid nitrogen. Brain tissue was homogenized with ethanol and chloroform. TXB2 and 6-keto-PGF1α in the homogenate were eluted using a C18 column and a silica cartridge. Levels were measured using specific radioimmunoassay kits. [1]

3 mg/kg Guinea pigs

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Mouse model of cerebral ischemia-reperfusion: Male ddy mice (25-35 g) were anesthetized with sodium thiopental (30 mg/kg i.v.). A thread was placed around each exposed common carotid artery, passed through a small polyethylene tube (0.5 mm i.d., ~7 mm length), and tied. The incision was sutured leaving tube ends and threads external. On the next day, under anesthesia, arteries were occluded by pulling each artery into the tube via the thread, fixed with a clip. Reperfusion was initiated by cutting the thread and removing the tube. For spontaneous locomotor activity assessment, mice were placed in activity wheel devices. One minute after intravenous drug administration, bilateral common carotid arteries were occluded for 10 min, then reperfusion started and wheel revolutions counted at various times. For motor coordination, a rotarod treadmill device was used. Mice that stayed on the rod for 100 s were selected. One minute after i.v. drug, arteries were occluded for 30 min, then after reperfusion mice were placed on the rod and number of falls in 100 s recorded. Ozagrel was dissolved in physiological saline and administered intravenously at 0.3-10 mg/kg. [1]
SHR rat model: Male spontaneously hypertensive rats (330-450 g) were subjected to two cycles of ischemia-reperfusion using the same occlusion method (two threads and tubes per artery). Bilateral common carotid arteries were occluded for 30 min, reperfused for 30 min, then occluded again for 30 min followed by second reperfusion. Ozagrel was administered subcutaneously twice (before each occlusion) at 1-10 mg/kg. Thirty minutes after start of second reperfusion, cerebral cortical specific gravity was measured using a bromobenzene-kerosene gradient column. [1]
Cat model: Cats (2.0-3.9 kg) of either sex were anesthetized with fluothane inhalation. A tracheal cannula was inserted and connected to a respirator. Femoral artery and vein catheters were placed for blood pressure monitoring and drug administration. Left orbital tissues and dorsolateral optic canal bone were removed, and left middle cerebral artery exposed via dural incision. A PO2 electrode was inserted into the middle eicosylvan cortex through a parietal bone hole. Cortical PO2 was recorded. Ozagrel was infused intravenously starting 30 min before middle cerebral artery occlusion (with a clip). Occlusion lasted 2 h, then clip was removed to start reperfusion. [1]

J Pharmacol Sci.2009 Oct;111(2):211-5;Pharmacology.1999 Nov;59(5):257-65.

Ozagrel belongs to the cinnamic acid class of drugs. Ozagrel has been used in clinical trials for the treatment of dry eye syndrome.

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Ozagrel is a selective thromboxane A2 synthetase inhibitor that suppresses the increase in TXA2 and increases PGI2 levels after cerebral ischemia-reperfusion. The improved motor outcomes and reduced brain edema are attributed to preservation of cerebral blood flow via vasodilation and inhibition of platelet aggregation, as well as prevention of postischemic hypoperfusion and edema formation. Unlike nizofenone, which increased cortical PO2 but did not prevent edema, ozagrel restored PO2 to pre-ischemic levels and reduced edema. Ozagrel has also shown efficacy in experimental and clinical subarachnoid hemorrhage for preventing vasospasm. [1]

C13H12N2O2

228.25

228.089

C, 68.41; H, 5.30; N, 12.27; O, 14.02

82571-53-7

Ozagrel sodium;189224-26-8;Ozagrel hydrochloride;78712-43-3

5282440

White to off-white solid powder

1.2±0.1 g/cm3

468.0±25.0 °C at 760 mmHg

223 - 224ºC

236.8±23.2 °C

0.0±1.2 mmHg at 25°C

1.593

1.65

1

3

4

17

283

0

C(N1C=NC=C1)C1C=CC(/C=C/C(=O)O)=CC=1

SHZKQBHERIJWAO-AATRIKPKSA-N

InChI=1S/C13H12N2O2/c16-13(17)6-5-11-1-3-12(4-2-11)9-15-8-7-14-10-15/h1-8,10H,9H2,(H,16,17)/b6-5+

(E)-3-(4-((1H-imidazol-1-yl)methyl)phenyl)acrylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)