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Sumatriptan
SUMATRIPTAN BASE · gr43175 · IMITREX · IMIGRAN · gr43175x · Sumatriptan · Imigran，Imitrex · SuMatriptan Maxalt
Identifikatoren & physikalische Daten
| CAS No. | 103628-46-2 |
|---|---|
| Summenformel | C14H21N3O2S |
| Durchschnittliche Molmasse | 295,4 g/mol |
| Monoisotopische Masse | 295,13544791 g/mol |
| SMILES | CNS(=O)(=O)Cc1ccc2[nH]cc(CCN(C)C)c2c1 |
| InChIKey | KQKPFRSPSRPDEB-UHFFFAOYSA-N |
| PubChem CID | 5358 |
| ChEMBL | CHEMBL128 |
| ChEBI | CHEBI:10650 |
| EC No. | 600-462-9 |
| DTXSID | DTXSID4023628 |
Chemische & physikalische Eigenschaften
| XLogP | 0,9 |
|---|---|
| Polarare Oberfläche (TPSA) | 73,6 |
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 4 |
| Frei drehbare Bindungen | 6 |
| Schwere Atome | 20 |
| Formalladung | 0 |
| Komplexität | 405 |
| Arzneimittel | PharmaceuticalsPharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | log Kow = 0.93 |
| Löslichkeit | 54mg/mL40.3 [ug/mL] (The mean of the results at pH 7.4)DMSO (Slightly), Methanol (Slightly)21.4 mg/mL |
| Human Drugs | Breast FeedingLactationMilk, HumanSerotonin Receptor AgonistsSerotonin 5-HT1 Receptor AgonistsTriptansVasoconstrictor AgentsFDA approved drugs -> Active ingredientPharmaceuticalsMedicines for acute migraine attacks |
| Schmelzpunkt | 169-170169-171 °C169 - 171 °C169-171°C |
| Physical Description | Solid |
| Dissociation Constants | 9.54.9 |
| Collision Cross Section | 162.1 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)] |
| Other Experimental Properties | MW: 413.49mp 165-166 °C /Sumatriptan succinate/ |
| Siedepunkt | 497.7±55.0 °C(Predicted) |
| Dichte | 1.1778 (rough estimate) |
| Brechungsindex | 1.6740 (estimate) |
| Lagerbedingungen | Refrigerator |
| Aggregatzustand | Solid |
| pKa (Säurekonstante) | pKa 9.5 (Uncertain) |
| Farbe | Off-White to Pale Yellow |
| Henry-Konstante | 2.2×108 mol/(m3Pa) at 25℃, HSDB (2015) |
| Hauptanwendungen | pharmaceutical |
| InChI | InChI=1S/C14H21N3O2S/c1-15-20(18,19)10-11-4-5-14-13(8-11)12(9-16-14)6-7-17(2)3/h4-5,8-9,15-16H,6-7,10H2,1-3H3 |
| InChIKey | KQKPFRSPSRPDEB-UHFFFAOYSA-N |
| SMILES | N1C2=C(C=C(CS(NC)(=O)=O)C=C2)C(CCN(C)C)=C1 |
| CAS Datenbank | 103628-46-2(CAS DataBase Reference) |
| NIST chemische Informationen | Sumatriptan(103628-46-2) |
| EPA chemische Informationen | 1H-Indole-5-methanesulfonamide, 3-[2-(dimethylamino)ethyl]-N-methyl- (103628-46-2) |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH319 (33.3%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]P203, P264+P265, P273, P280, P305+P351+P338, P318, P337+P317, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 6 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Sumatriptan: Does not have an individual approval but may be used under an appropriate group standard |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl sumatriptan, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl sumatriptan succinate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Sumatriptan succinate/ |
| Hazard Classes and Categories | Eye Irrit. 2 (33.3%) |
| Lagerbedingungen | Sumatriptan succinate injection and tablets and sumatriptan nasal spray should be protected from light and stored at 2-30 °C. |
| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Wechselwirkungen | Alcohol consumed 30 minutes prior to sumatriptan ingestion had no effect on the pharmacokinetics of sumatriptan.Due to gut and hepatic metabolic first-pass effects, the increase of systemic exposure after coadministration of an MAO-A inhibitor with oral sumatriptan is greater than after coadministration of the monoamine oxidase inhibitors (MAOI) with subcutaneous sumatriptan. In a study of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous sumatriptan. Under the conditions of this experiment, the result was a 2-fold increase in the area under the sumatriptan plasma concentration x time curve (AUC), corresponding to a 40% increase in elimination half-life. This interaction was not evident with an MAO-B inhibitor. A small study evaluating the effect of pretreatment with an MAO-A inhibitor on the bioavailability from a 25-mg oral sumatriptan tablet resulted in an approximately 7-fold increase in systemic exposure.Sumatriptan tablets and any ergotamine-containing or ergot-type medication (like dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor should sumatriptan and another 5-HT1 agonists.A 65-year-old woman was referred with confusion, strange behavior, sinus tachycardia, hypertension and hyperthermia. She had been taking sumatriptan and paroxetine and recovered completely after discontinuation of these agents. The diagnosis was 'serotonin syndrome', a result of overstimulation of 5-HT(1A) receptors in the raphe nuclei of the brainstem. It is a complication of the use of serotonergic agents and is associated with the rapid onset of mental, autonomic and neurological symptoms. Treatment consists of discontinuation of the suspected medication and, in severe cases, providing symptomatic relief. ... |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a log Kow of 0.93(2) and a regression-derived equation(3), indicates that sumatriptan is expected to have high mobility in soil(SRC). However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(4,5), suggesting that mobility may be much lower in some soils. Volatilization of sumatriptan from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.5X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Sumatriptan is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.1X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(7). Biodegradation data were not available(SRC, 2009).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a log Kow of 0.93(2) and a regression-derived equation(3), indicates that sumatriptan is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.5X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2009).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sumatriptan, which has an estimated vapor pressure of 7.1X10-8 mm Hg at 25 °C is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase sumatriptan may be removed from the air by wet or dry deposition(SRC). Sumatriptan does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| Unerwünschte Wirkungen | The safety of treating more than 4 headaches in a month with sumatriptan has not been investigated yet. Notably, adverse reactions to sumatriptan are influenced by the dosage and can be dose-dependent. Individuals experiencing nausea and vomiting can opt for subcutaneous injection instead of the oral form of sumatriptan. However, it is noteworthy that subcutaneous administration of the drug is associated with a higher occurrence of adverse events. |
| Expositionspfade | Subcutaneous, Oral, Nasal, Transdermal |
| Milk Concentrations | Sumatriptan is distributed into milk in humans and animalsin animals, sumatriptan concentrations are eight-fold higher than concurrent maternal plasma concentrations. In a limited number of healthy lactating women, the total recovery of sumatriptan in breast milk averaged 0.24% of a single 6-mg subcutaneous dose, corresponding to an average infant exposure of 3.5% of the maternal dose on a weight-adjusted basis.The excretion of a 6 mg subcutaneous dose of sumatriptan in breast milk was studied in five lactating volunteer subjects with a mean age of 27.6 years and a mean body weight of 75 kg. Drug concentrations in milk and plasma over the ensuing 8 hr were measured by high-performance liquid chromatography. The mean milk:plasma ratio estimated from the areas under the milk and plasma concentration-time curves (AUC) was 4.9 (95% CI 4.1-5.7), indicating a significant transfer of sumatriptan into the milk compartment. The mean total recovery of drug in milk was estimated to be only 14.4 ug (95% CI 6.1-22.7 ug), or 0.24% of the 6 mg administered dose. On a weight-adjusted basis this corresponded to a mean infant exposure of 3.5% of the maternal dose (95% CI 0.3-6.7%). If oral bioavailability in the infant is similar to that in adults (14%), the weight-adjusted infant dose is reduced to 0.49%. Furthermore, allowance for reduced clearance in the infant predicts an infant exposure varying from 4.9% in a very premature neonate to 0.7% in a 30 week old infant. Since sumatriptan is usually administered as a single dose at infrequent intervals, the low level of excretion in breast milk suggests that continued breast feeding following its use will not pose a significant risk to the suckling infant. Even this minor exposure could be largely avoided by expressing and discarding all milk for 8 hr after the dose. |
| Toxizitätsübersicht | The available data concerning sumatriptan overdose and toxicity are limited. A case report highlights a male patient aged 36 who self-reported excessive use of sumatriptan, administering 66 subcutaneous injections of 6 mg within 4 weeks. No adverse reactions were clinically observed, and laboratory parameters remained unaffected.The 5-HT<sub>1B</sub> and 5-HT<sub>1D</sub> receptors function as autoreceptors, which inhibit the firing of serotonin neurons and a reduction in the synthesis and release of serotonin upon activation. After sumatriptan binds to these receptors, adenylate cyclase activity is inhibited via regulatory G proteins, incrases intracellular calcium, and affects other intracellular events. This results in vasoconstriction and inhibtion of sensory nociceptive (trigeminal) nerve firing and vasoactive neuropeptide release. Sumatriptan stimulates 5-HT receptors of the 1D subtype, most likely presynaptic receptors, resulting in selective vasoconstriction of inflamed and dilated cranial blood vessels in the carotid circulation. Sumatriptan also blocks the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater during migraine and may inhibit the release of inflammatory mediators from the trigeminal nerve. |
| Signs and Symptoms | Symptoms of overdose include convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation. |
| Soil Adsorption/Mobility | The Koc of sumatriptan is estimated as 80(SRC), using a log Kow of 0.93(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that sumatriptan is expected to have high mobility in soil. However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(4,5), suggesting that mobility may be much lower in some soils(SRC). |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ The excretion of a 6 mg subcutaneous dose of sumatriptan in breast milk was studied in five lactating volunteer subjects with a mean age of 27.6 years and a mean body weight of 75 kg. Drug concentrations in milk and plasma over the ensuing 8 hr were measured by high-performance liquid chromatography. The mean milk:plasma ratio estimated from the areas under the milk and plasma concentration-time curves (AUC) was 4.9 (95% CI 4.1-5.7), indicating a significant transfer of sumatriptan into the milk compartment. The mean total recovery of drug in milk was estimated to be only 14.4 ug (95% CI 6.1-22.7 ug), or 0.24% of the 6 mg administered dose. On a weight-adjusted basis this corresponded to a mean infant exposure of 3.5% of the maternal dose (95% CI 0.3-6.7%). If oral bioavailability in the infant is similar to that in adults (14%), the weight-adjusted infant dose is reduced to 0.49%. Furthermore, allowance for reduced clearance in the infant predicts an infant exposure varying from 4.9% in a very premature neonate to 0.7% in a 30 week old infant. Since sumatriptan is usually administered as a single dose at infrequent intervals, the low level of excretion in breast milk suggests that continued breast feeding following its use will not pose a significant risk to the suckling infant. Even this minor exposure could be largely avoided by expressing and discarding all milk for 8 hr after the dose./HUMAN EXPOSURE STUDIES/ Patients (N = 670) have received single oral doses of 140 to 300 mg without significant adverse effects. Volunteers (N = 174) have received single oral doses of 140 to 400 mg without serious adverse events./SIGNS AND SYMPTOMS/ Cerebral angiopathy of the postpartum period is a rare entity, sometimes promoted by vasoconstrictives drug prescription. Its clinical presentation includes headaches, seizures and focal neurological deficits, which develop shortly after a normal pregnancy. The diagnosis is based on clinical findings and angiography, showing multiple narrowing of the intracranial cerebral arteries. This neurological feature is reversible and the clinical outcome is good. We report a case of benign cerebral angiopathy in a 20-year-old woman in the postpartum period, occurring after administration of sumatriptan and ergot derivates./SIGNS AND SYMPTOMS/ Other arrhythmias or ECG abnormalities reported infrequently in patients receiving sumatriptan therapy include bradycardia, tachycardia, nonspecific ST or T wave changes, prolongation of PR or QTC intervals, sinus arrhythmias, abnormal P waves with nodal rhythm, QRS/T-axis deviations, nonsustained ventricular premature complexes, isolated junctional ectopic beats, atrial ectopic beats, and delayed activation of the right ventricle.For more Human Toxicity Excerpts (Complete) data for Sumatriptan (21 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Sumatriptan's production and use as a migraine medication(1) may result in its release to the environment through various waste streams(SRC). |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)sumatriptanDILI NegativeOralDOI:10.1016/j.drudis.2019.09.022 |
| Wassergefährdungsklasse (WGK) | 3 |
| Zollcode | 2935904000 |
| R-Sätze (R) | 36/37/38 |
| Gefahrensymbole | Xi |
| Sicherheitshinweise (S) | 26 |
| Lagerklasse | 13 - Non Combustible Solids |
| Gefahrstoffdaten | 103628-46-2(Hazardous Substances Data) |
| Gefahrenklasse | Aquatic Chronic 3Repr. 2 |
Anwendungen & Verwendung
Verwenden
Sumatriptan is a serotonin 5HT1-receptor agonist.