CAS 78415-72-2|Milrinone
Introduction：Basic information about CAS 78415-72-2|Milrinone, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | Milrinone | ||
|---|---|---|---|
| CAS Number | 78415-72-2 | Molecular Weight | 211.219 |
| Density | 1.3±0.1 g/cm3 | Boiling Point | 448.7±45.0 °C at 760 mmHg |
| Molecular Formula | C12H9N3O | Melting Point | >3000C |
| MSDS | USA | Flash Point | 225.2±28.7 °C |
| Symbol | GHS06 | Signal Word | Danger |
Names
| Name | milrinone |
|---|---|
| Synonym | More Synonyms |
Milrinone BiologicalActivity
| Description | Milrinone is a PDE3 inhibitor, and also an inotrope and vasodilator. |
|---|---|
| Related Catalog | Signaling Pathways >>Metabolic Enzyme/Protease >>Phosphodiesterase (PDE)Research Areas >>Cardiovascular Disease |
| In Vitro | Milrinone (1 µM) increases PKA activity in hypoxic myocytes to normoxic levels. Milrinone (50 nM) normalizes TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation[1]. Milrinone significantly reduces NE-induced vasoconstriction, attenuating both NE sensitivity and maximal tension generation. Inhibition of ATP-sensitive K+ channels or voltage-gated K+ channels do not prevent the milrinone-induced attenuation of NE responses[4]. |
| In Vivo | Milrinone (1 μg/kg/min, i.v.) significantly reduces PAP, PVR (−18.96 ± 1.7%), and LAP (−26.03 ± 2.3%) in congestive heart failure (CHF) rats. Milrinone (1 mg/mL, inhalation) results in a near-maximal reduction of PAP without significant effects on AP, decreases pulmonary artery pressure similarly in a larger collective of CHF rats. Milrinone inhalation selectively increases cAMP but not cGMP plasma concentrations in both groups. Repeated milrinone inhalations even reduce lung wet/dry weight ratio[2]. Milrinone (49.5 μg) largely shifts the ESPVR upwards and significantly increases end-systolic pressure (ESP(0.08)) and the systolic pressure-volume area (PVA(0.08)) at a mid-range LV volume (0.08 mL/g myocardium). Milrinone also slightly decreases LV ESP(ESV) and decreased Ea[3]. |
| Animal Admin | In juvenile rats of 100 ± 8 g body weight (bw), CHF is induced by supracoronary aortic banding. In brief, rats are anesthetized by intraperitoneal injection of ketamine (87 mg/kg bw) and xylazine (13 mg/kg bw). Rats are placed in the supine position, the chest wall is shaved, and a left thoracotomy is performed in the third intercostal space during ventilation with 100% O2. The ascending aorta is freed from connective tissue and partially occluded by implantation of a titanium clip with a defined internal diameter of 0.8 mm. After surgical closure of the thorax, the rats are allowed to recover from anesthesia. For postoperative analgesia, rats receive 250 mg/kg bw of metamizole intramuscularly immediately after the operation and on the first postoperative day. Sham-operated rats serve as controls. After recovery from anesthesia, the animals are placed in cages with free access to water and standard laboratory diet. For inhalation, milrinone (0.2-5 mg/mL) or NaCl (0.9%) are nebulized using an ultrasonic nebulizer and inhaled for 3 min at identical peak inspiratory pressures as used throughout the experiment. A 3-min nebulization of 1 mg/mL milrinone results in vaporization of 14 μg of the phosphodiesterase-3 inhibitor as determined by microgravimetry. Therefore, the respective dose of 39 μg/kg is analog to inhaled doses in human studies. For intravenous delivery, milrinone (initial bolus of 2-10 μg/kg, followed by 0.2-1 μg/kg/min) or equivalent volumes of NaCl (0.9%; initial bolus of 1.6 mL/kg, followed by 10 μL/kg/h) are administered by an infusion pump for 10 min. |
| References | [1]. Santhosh KT, et al. Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes. Br J Pharmacol. 2011 Jul;163(6):1223-36. [2]. Hentschel T, et al. Inhalation of the phosphodiesterase-3 inhibitor milrinone attenuates pulmonary hypertension in a rat model of congestive heart failure. Anesthesiology. 2007 Jan;106(1):124-31. [3]. Kishi T, et al. Effects of milrinone on left ventricular end-systolic pressure-volume relationship of rat hearts in situ. Clin Exp Pharmacol Physiol. 2001 Sep;28(9):737-42. [4]. Taylor MS, et al. Effect of milrinone on small mesenteric artery vasoconstriction: role of K(+) channels. Am J Physiol. 1999 Jul;277(1 Pt 1):G69-78. |
Chemical & Physical Properties
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 448.7±45.0 °C at 760 mmHg |
| Melting Point | >3000C |
| Molecular Formula | C12H9N3O |
| Molecular Weight | 211.219 |
| Flash Point | 225.2±28.7 °C |
| Exact Mass | 211.074554 |
| PSA | 69.54000 |
| LogP | 0.41 |
| Vapour Pressure | 0.0±1.1 mmHg at 25°C |
| Index of Refraction | 1.622 |
| InChIKey | PZRHRDRVRGEVNW-UHFFFAOYSA-N |
| SMILES | Cc1[nH]c(=O)c(C#N)cc1-c1ccncc1 |
| Storage condition | 2-8°C |
| Stability | Stable. Incompatible with strong oxidizing agents. |
| Water Solubility | DMSO: >10 mg/mL |
Toxicological Information
CHEMICAL IDENTIFICATION |
ACUTE TOXICITY DATA - TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 91 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 58 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 27,652,1996
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 73 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 137 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 62 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 27,652,1996
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 79 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- LD - Lethal dose
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- >25 mg/kg
- TOXIC EFFECTS :
- Behavioral - somnolence (general depressed activity) Cardiac - other changes Lungs, Thorax, or Respiration - fibrosis, focal (pneumoconiosis)
- REFERENCE :
- YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 21,2891,1993
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 40 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 44400 ug/kg
- TOXIC EFFECTS :
- Behavioral - ataxia Cardiac - cardiomyopathy including infarction Lungs, Thorax, or Respiration - dyspnea
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985 ** OTHER MULTIPLE DOSE TOXICITY DATA **
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 4550 mg/kg/13W-I
- TOXIC EFFECTS :
- Behavioral - muscle weakness Gastrointestinal - changes in structure or function of salivary glands
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 11375 mg/kg/65W-I
- TOXIC EFFECTS :
- Related to Chronic Data - death
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 1200 mg/kg/30D-I
- TOXIC EFFECTS :
- Cardiac - cardiomyopathy including infarction Kidney, Ureter, Bladder - changes in bladder weight Related to Chronic Data - death
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 14560 mg/kg/1Y-I
- TOXIC EFFECTS :
- Blood - pigmented or nucleated red blood cells Nutritional and Gross Metabolic - other changes
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 910 mg/kg/13W-I
- TOXIC EFFECTS :
- Cardiac - cardiomyopathy including infarction Cardiac - pulse rate increase, without fall in BP Cardiac - changes in heart weight
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 60 mg/kg/2W-I
- TOXIC EFFECTS :
- Cardiac - cardiomyopathy including infarction Cardiac - EKG changes not diagnostic of specified effects Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases
- REFERENCE :
- NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 3,245,1985
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 455 mg/kg/13W-I
- TOXIC EFFECTS :
- Lungs, Thorax, or Respiration - fibrosis, focal (pneumoconiosis)
- REFERENCE :
- YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 21,2891,1993
Safety Information
| Symbol | GHS06 |
|---|---|
| Signal Word | Danger |
| Hazard Statements | H301 + H311 + H331 |
| Precautionary Statements | Missing Phrase - N15.00950417-P261-P280-P302 + P352 + P312-P304 + P340 + P312-P403 + P233 |
| Personal Protective Equipment | Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges |
| Hazard Codes | T:Toxic |
| Risk Phrases | R23/24/25 |
| Safety Phrases | S36/37/39-S45 |
| RIDADR | UN 2811 6.1/PG 3 |
| WGK Germany | 3 |
| RTECS | DW1762000 |
| Packaging Group | III |
| Hazard Class | 6.1(b) |
| HS Code | 2933399090 |
Customs
| HS Code | 2933399090 |
|---|---|
| Summary | 2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |
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Synonyms
| 6-Hydroxy-2-methyl-3,4'-bipyridine-5-carbonitrile |
| EINECS 278-903-6 |
| MFCD00133539 |
| 1,6-dihydro-2-methyl-6-oxo-(3,4′-bipyridine)-5-carbonitrile |
| Milrinonum |
| 1,6-Dihydro-2-methyl-6-oxo-(3,4'-bipyridine)-5-carbonitrile |
| Milrila |
| Milrinone |
| 1,2-Dihydro-6-methyl-2-oxo-5-(4-pyridinyl)nicotinonitrile |
| 6-methyl-2-oxo-5-pyridin-4-yl-1H-pyridine-3-carbonitrile |
| [3,4'-Bipyridine]-5-carbonitrile, 6-hydroxy-2-methyl- |
| Corotrope |
| Milrinona |
| Primacor |
| Corotrop |
| 2-Methyl-6-oxo-1,6-dihydro-3,4'-bipyridine-5-carbonitrile |
| [3,4'-Bipyridine]-5-carbonitrile, 1,6-dihydro-2-methyl-6-oxo- |
