化工社化工社 化学情報印刷レポート · 研究参考用
フェンタニル
N-フェニル-N-(1-フェネチル-4-ピペリジニル)プロパンアミド · フェンタネスト · N-フェニル-N-[1-(2-フェニルエチル)ピペリジン-4-イル]プロパンアミド · N-フェニル-N-(1-フェネチルピペリジン-4-イル)プロパンアミド · N-フェニル-N-[1-(2-フェニルエチル)-4-ピペリジニル]プロパンアミド · デュロテップ-MT · デュロテップ · N-フェニル-N-(1-フェネチルピペリジン-4-イル)プロピオンアミド
識別子と物理属性
| CAS No. | 437-38-7 |
|---|---|
| 分子式 | C22H28N2O |
| 平均分子量 | 336.5 g/mol |
| 単同位体質量 | 336.22016352 g/mol |
| SMILES | CCC(=O)N(c1ccccc1)C1CCN(CCc2ccccc2)CC1 |
| InChIKey | PJMPHNIQZUBGLI-UHFFFAOYSA-N |
| PubChem CID | 3345 |
| ChEMBL | CHEMBL596 |
| ChEBI | CHEBI:119915 |
| EC No. | 207-113-6 |
| DTXSID | DTXSID9023049 |
| 現地名 | フェンタニル |
化学・物理的性質
| XLogP | 4 |
|---|---|
| 極性表面積 | 23.6 |
| 水素結合供与体数 | 0 |
| 水素結合受容体数 | 2 |
| 回転可能結合数 | 6 |
| 重原子数 | 25 |
| 形式電荷 | 0 |
| 複雑度 | 391 |
| 物質分類 | Other Uses -> Pharmaceuticals-> NIOSH Emergency Response Categories |
| 医薬品 | DEA NFLIS-Drug Category -> Fentanyl and Fentanyl-relatedDEA Schedule II Controlled Substance -> OpiatesPharmaceuticals -> Analgesics (Anesthetics)Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds |
| LogP（分配係数） | log Kow = 4.053.9 |
| Color/Form | Crystals |
| 溶解度 | 0.74mg/mLIn water, 200 mg/L at 25 °C2.40e-02 g/L水にほとんど溶けず、エタノール (96%) およびメタノールに溶けやすい0.2g/L(25℃) |
| Human Drugs | Breast FeedingLactationMilk, HumanAnalgesics, OpioidNarcoticsAnesthetics, IntravenousOpiatesFDA approved drugs -> Active ingredientEMA approved medicines: Human medicinePharmaceuticals |
| Animal Drugs | Active Ingredients (Fentanyl) -> FDA Greenbook |
| Decomposition | When heated to decomposition it emits toxic fumes of /nitrogen oxides/. |
| 融点 | 83-8485.2 °CWhite crystalline powderMP: 149-151 °Cbitter taste. Soluble in methanolslightly soluble in chloroform /Fentanyl citrate/87.5 °C83-84°C |
| 蒸気圧 | 4.43X10-9 mm Hg at 25 °C (estrapolated) |
| Physical Description | SolidCrystals or crystalline powder. |
| Dissociation Constants | 8.438.99pKa = 7.3OdorlesspKa: 8.3 /Fentanyl citrate/ |
| 沸点 | 466℃ |
| 密度 | 1.087 |
| 屈折率 | 1.6500 (estimate) |
| 引火点 | 186℃ |
| 貯蔵条件 | Controlled Substance, -20°C Freezer |
| pKa（酸解離定数） | 8.4(at 25℃) |
| 外観・状態 | A crystalline solid |
| 色 | クリスタル |
| ヘンリー定数 | 1.1×106 mol/(m3Pa) at 25℃, HSDB (2015) |
| 安定性 | Hygroscopic |
| 主な用途 | 医薬品（低分子化合物） |
| InChI | 1S/C22H28N2O/c1-2-22(25)24(20-11-7-4-8-12-20)21-14-17-23(18-15-21)16-13-19-9-5-3-6-10-19/h3-12,21H,2,13-18H2,1H3 |
| InChIKey | PJMPHNIQZUBGLI-UHFFFAOYSA-N |
| SMILES | N2(CCC(CC2)N(c3ccccc3)C(=O)CC)CCc1ccccc1 |
| EPAの化学物質情報 | Propanamide, N-phenyl-N-[1-(2-phenylethyl)-4-piperidinyl]- (437-38-7) |
化学的特性
フェンタニルは強力な合成オピオイド鎮痛剤であり主に痛みの管理に用いられます化学式はC22H28N2Oと表されモルヒネよりも約50から100倍の鎮痛効果があるとされていますこの物質は手術後の激しい痛みの緩和や慢性痛患者の痛み管理プログラムの一環として使用されることが多いです
化学的特性
Pale Brown Solid
安全性と法規制
| GHS 分類 | DangerH300 (98.7%): Fatal if swallowed [Danger Acute toxicity, oral]P203, P233, P260, P261, P262, P263, P264, P270, P271, P272, P273, P280, P284, P301+P316, P302+P352, P304+P340, P316, P318, P320, P321, P330, P333+P317, P342+P316, P361+P364, P362+P364, P403, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 77 reports by companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 規制情報 | DEA schedule II controlled substanceFentanyl: HSNO Approval: HSR007044 Approved with controls |
| その他の安全情報 | - Indoor Air: Fentanyl can be released into indoor air as fine particles or liquid spray (aerosol). |
| 有害性の概要 | Fentanyl is a solid. It is a Schedule II controlled substance. Fentanyl citrate is a strong analgesic used preoperatively, during surgery, and in the immediate postoperative period for its analgesic action. . . . Introduced into clinical practice in the 1960s, the analgesic fentanyl is 100 times more potent than morphine. [HSDB] TLV Basis is CNS impairment and respiratory depression[ACGIH TLVs and BEIs] |
| FDA 要件 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including fentanyl, 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 identifies currently marketed prescription drug products, including fentanyl citrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Fentanyl citrate/The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Fentanyl is included on this list.Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Opiates. Unless specifically excepted or unless in another schedule any of the following opiates, including its isomers, esters, ethers, salts and salts of isomers, esters and ethers whenever the existence of such isomers, esters, ethers, and salts is possible within the specific chemical designation, dextrorphan and levopropoxyphene excepted:. Fentanyl (DEA Code Number: 9801) is included on this list.Ophthalmic and topical dosage form new animal drugs. Fentanyl. ... Indications for use. For the control of postoperative pain associated with surgical procedures in dogs. ... Limitations. Fentanyl is a Class II controlled substance. Observe all "black-box warnings" on product labeling. Federal law restricts this drug to use by or on the order of a licensed veterinarian. |
| Explosion Hazards | - |
| Special Reports | DHHS/NIDAResearch Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability (1984) DHHS Pub No. (ADM)87-1332Research Monograph Series 54: Mechanisms of Tolerance and Dependence (1984) DHHS Pub No. (ADM)88-1330Research Monograph Series 56: Etiology of Drug Abuse: Implications for Prevention (1987) DHHS Pub No. (ADM)87-1335Research Monograph Series 59: Current Research on the Consequences of Maternal Drug Abuse (1985) DHHS Pub No. (ADM)85-1400For more Special Reports (Complete) data for Fentanyl (10 total), please visit the HSDB record page. |
| Chemical Dangers | - Hazardous polymerization will not occur. |
| History and Incidents | On October 23, 2002, in the middle of an evening performance at a Moscow music theater, some 50 Chechen terrorists equipped with firearms as well as large quantities of explosives suddenly seized the venue and the 800 people inside. The terrorists threatened to kill everyone inside unless Russia ended the war in Chechnya. Although the Chechen militants agreed to release some of the hostages during the first couple of days, negotiations with the Russian authorities eventually stalled. Just before dawn on October 26, Russian special police units resorted to using an incapacitating gas based on the drug fentanyl to end the crisis. All of the Chechen militants were killed, and most of the civilian captives survived. But while the operation was largely a success, at least 117 of the hostages died from the effects of the gas. /Incapacitating gas based on the drug fentanyl/ |
| Hazard Classes and Categories | Acute Tox. 2 (98.7%) |
| 消火 | - Burning may produce carbon monoxide, carbon dioxide, and nitrogen oxides. |
| 処分方法 | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. |
| Threshold Limit Values (TLV) | 0.00001 [mg/m3], inhalable particulate matter (Surface Level = 1 ug/100cm2)0.00002 [mg/m3], inhalable particulate matter |
| Effects of Short Term Exposure | It is unknown whether chronic or repeated exposure to fentanyl increases the risk of carcinogenicity, reproductive toxicity, or developmental toxicity. |
| Personal Protective Equipment (PPE) | GENERAL INFORMATION |
| 体内負荷 | The concentration of fentanyl excreted in sweat was 0.17-10.2 ng/uL in persons treated with a total daily dose of 600 ug(1).... Following an observed spike of heroin-fentanyl related deaths in Melbourne, Australia, a study was undertaken to determine the prevalence of these cases. All reportable deaths occurring in Victoria during 2015 and submitted to the toxicology laboratory were analysed using LC-MS-MS to confirm the combination of the heroin marker 6-acetylmorphine and/or morphine, and fentanyl. Over 4,000 coronial cases in 2015 underwent toxicological analysis for these drugs, there were nine cases identified that involved fentanyl-laced heroin. ... The ages ranged from 25 to 57 years with an average of 40 and median of 37 years, and consisted of eight males and one female. The average and median femoral blood concentration of fentanyl was 18 and 20 ng/mL (range: <1-45 ng/mL), and morphine 140 and 80 ng/mL (range: 20-400 ng/mL), respectively. All nine cases had 6-acetylmorphine detectable in blood. Urine analysis was also performed where available. ...... Here we report two cases of fatal intravenous injection of the content from fentanyl patches. Both were male drug addicts, found dead within a one week interval in the same apartment. Post-mortem femoral blood was screened for amphetamines, cannabinoids, cocaine, and opioids with immunological methods (EMIT II) and further with headspace gas chromatography for alcohol and with liquid chromatography mass spectrometry (LC-MS) for different drugs, including fentanyl. ... In the first case, the toxicological analysis revealed fentanyl (2.7 ng/mL), morphine (31.4 ng/mL), and ethanol (1.1 g/L) in postmortem blood and amphetamine, cannabinoids, morphine, and ethanol (1.4 g/L) in postmortem urine. In the second case, the analysis revealed fentanyl (13.8 ng/mL), 7-aminoclonazepam (57.1 ng/mL), and sertralin (91.9 ng/mL) in postmortem blood and a small amount of ethanol (0.1 g/L) in postmortem urine. ...In 2013 and 2014, more than 700 deaths were attributed to fentanyl and fentanyl analogs in the United States. Of recent concern is the cluster of unintentional fentanyl overdoses because of tablets thought to be "Norco" purchased on the street in Northern California. U-47700 (trans-3,4-dichloro-N-[2-(dimethyl-amino)cyclohexyl]-N-methylbenz-amide) is a nonfentanyl-based synthetic opioid with 7.5 times the binding affinity of morphine to mu-opioid. We report a case of fentanyl and U-47700 intoxication from what was thought to be illicitly purchased Norco. A 41-year-old woman presented to the emergency department (ED) for altered mental status shortly after ingesting 3 beige Norco pills bearing a Watson imprint. She had pinpoint pupils and respiratory depression, which reversed after 0.4 mg naloxone administration intravenously. She had complete recovery and was discharged from the ED after a 4-hour observation period. Serum testing with liquid chromatography-quadrupole time-of-flight mass spectrometry (LC 1260 QTOF/MS 6550Agilent, Santa Clara, CA) confirmed the presence of the medications the patient reported receiving, and additionally fentanyl (15.2 ng/mL) and U-47700 (7.6 ng/mL). In this case report, street Norco purchased in Central California resulted in altered mental status requiring naloxone reversal because of fentanyl and the novel synthetic opioid U-47700. Because these compounds are not detected by routine urine drug testing and physical examination findings are similar to those of a traditional opioid toxidrome, emergency providers should use the patient's history and other circumstantial details to aid in diagnosis. In cases with suspicion of opioid or opioid analogue cause, we recommend that emergency providers contact their local poison control center, medical toxicologist, or public health department to aid in the investigation.For more Body Burden (Complete) data for Fentanyl (16 total), please visit the HSDB record page. |
| Treatment | For the management of hypoventilation, immediate countermeasures include removing the Fentanyl and physically or verbally stimulating the patient. These actions can be followed by administration of a specific narcotic antagonist such as naloxone. The duration of hypoventilation following an overdose may be longer than the effects of the narcotic antagonist's action (the half-life of naloxone ranges from 30 to 81 minutes). The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after system removalrepeated administration of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and the release of catecholamines. Always ensure a patent airway is established and maintained, administer oxygen and assist or control respiration as indicated and use an oropharyngeal airway or endotracheal tube if necessary. Adequate body temperature and fluid intake should be maintained. (L1712) |
| 相互作用 | Serotonin syndrome is a syndrome identified by a triad of altered mental status, neuromuscular overactivity, and autonomic instability caused by the overstimulation of serotonin in the central nervous system and periphery. Serotonin syndrome may be provoked with the addition or increase in serotonergic agents such as selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors as well as other agents with serotonergic properties. Some narcotics, including fentanyl and methadone, have these properties and may be associated with the development of serotonin syndrome when used in conjunction with other agents. Currently, there are no identified case reports of narcotics as the sole agent causing serotonin syndrome. This report provides a brief overview of serotonin syndrome, particularly with cases involving administration of narcotics such as fentanyl and methadone. The case described is the first report associated with fentanyl and methadone without the coadministration of other serotonergic agents, and a possible drug interaction with voriconazole is discussed. This raises awareness of using multiple serotonergic narcotics and the potential precipitation of serotonin syndrome.There is an unmet clinical need to develop a pharmacological therapy to counter opioid-induced respiratory depression without interfering with analgesia or behavior. Several studies have demonstrated that 5-HT1A receptor agonists alleviate opioid-induced respiratory depression in rodent models. However, there are conflicting reports regarding their effects on analgesia due in part to varied agonist receptor selectivity and presence of anesthesia. Therefore the authors performed a study in rats with befiradol (F13640 and NLX-112), a highly selective 5-HT1A receptor agonist without anesthesia. Respiratory neural discharge was measured using in vitro preparations. Plethysmographic recording, nociception testing, and righting reflex were used to examine respiratory ventilation, analgesia, and sedation, respectively. Befiradol (0.2 mg/kg, n = 6) reduced fentanyl-induced respiratory depression (53.7 +/- 5.7% of control minute ventilation 4 min after befiradol vs. saline 18.7 +/- 2.2% of control, n = 9P < 0.001), duration of analgesia (90.4 +/- 11.6 min vs. saline 130.5 +/- 7.8 minP = 0.011), duration of sedation (39.8 +/- 4 min vs. saline 58 +/- 4.4 minP = 0.013)and induced baseline hyperventilation, hyperalgesia, and "behavioral syndrome" in nonsedated rats. Further, the befiradol-induced alleviation of opioid-induced respiratory depression involves sites or mechanisms not functioning in vitro brainstem-spinal cord and medullary slice preparations. The reversal of opioid-induced respiratory depression and sedation by befiradol in adult rats was robust, whereas involved mechanisms are unclear. However, there were adverse concomitant decreases in fentanyl-induced analgesia and altered baseline ventilation, nociception, and behavior.Chlorpromazine is used concurrently with meperidine to enhance its analgesic effect. However, such concurrent use ... may enhance & prolong the respiratory depression produced by meperidine. ... Fentanyl ... /has/ been reported to interact with promethazine /and may produce similar effects/.Droperidol does not produce analgesia but is a potent neuroleptic agent. It has been suggested that each compound in the droperidol-fentanyl mixture exerts its own pharmacologic action without any well defined antagonistic or potentiating actions. However, there is one exceptiondroperidol enhances the analgesic potency of fentanyl through a potentiative rather than an additive effect, the mechanism of which is unknown.For more Interactions (Complete) data for Fentanyl (24 total), please visit the HSDB record page. |
| 健康影響 | Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose. |
| 環境中動態 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 39,600(SRC), determined from a structure estimation method(2), indicates that fentanyl is expected to be immobile in soil. The pKa of fentanyl is 7.3(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the cation from moist soil is not expected because cations do not volatilize(SRC). Volatilization of the neutral form of fentanyl from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.8X10-12 atm-cu m/mole(SRC), based upon its vapor pressure, 4.43X10-9 mm Hg(5), and water solubility, 200 mg/L(6). Fentanyl is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(5). Biodegradation data in soil were not available(SRC, 2017).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 39,600(SRC), determined from a structure estimation method(2), indicates that fentanyl is expected to adsorb to suspended solids and sediment(SRC). A pKa of 7.3(3) indicates fentanyl will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization of the cation from water surfaces is not expected(SRC). Volatilization from water surfaces of neutral fentanyl is not expected(4) based upon an estimated Henry's Law constant of 9.8X10-12 atm-cu m/mole(SRC), from its vapor pressure, 4.43X10-9 mm Hg(5), and water solubility, 200 mg/L(6). Fentanyl is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). According to a classification scheme(7), an estimated BCF of 220(SRC), from a log Kow of 4.05(8) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high. Biodegradation data in water were not available(SRC, 2017).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), fentanyl, which has a vapor pressure of 4.43X10-9 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase fentanyl may be removed from the air by wet and dry deposition(SRC). Fentanyl contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| 有害作用 | ACGIH Carcinogen - Not Classifiable.Fentanyl's side effects are similar to those of heroin, which produce euphoria, confusion, respiratory depression (which, if extensive and untreated, may lead to arrest), drowsiness, nausea, visual disturbances, dyskinesia, hallucinations, delirium, a subset of the latter known as "narcotic delirium," analgesia, constipation, narcotic ileus, muscle rigidity, constipation, addiction, loss of consciousness, hypotension, coma, and even death. Alcohol and other drugs (ie, cocaine, heroin) can synergistically exacerbate fentanyl's side effects, creating multi-layered clinical scenarios that can be complex to manage. These substances, taken together, generate undesirable conditions that complicate the patient's prognosis. |
| 暴露経路 | Fentanyl can be absorbed into the body via inhalation, oral exposure or ingestion, or skin contact. It is not known whether fentanyl can be absorbed systemically through the eye. Fentanyl can be administered intravenously (IV), intramuscularly (IM), or as a skin patch (transdermally).Epiduralparental (transdermal, intramuscular). |
| 毒性の概要 | IDENTIFICATION AND USE: Fentanyl is a solid. It is a Schedule II controlled substance. Fentanyl citrate is a strong analgesic used preoperatively, during surgery, and in the immediate postoperative period for its analgesic action. In addition, the drug may be used to prevent or relieve tachypnea and postoperative emergence delirium. HUMAN STUDIES: Introduced into clinical practice in the 1960s, the analgesic fentanyl is 100 times more potent than morphine. Various methods of administration exist including the transdermal patch system, widely used in chronic pain and palliative care settings. Numerous, often imaginative methods of abuse of fentanyl patches have been reported, the majority of fatal fentanyl overdose cases resulting from deliberate abuse or suicide. The most serious adverse effect of fentanyl is respiratory depression. Fentanyl should be administered only under the supervision of qualified clinicians. Patients receiving fentanyl should be advised of the importance of taking the drug exactly as prescribed. Skeletal and thoracic muscle rigidity occurs frequently, especially following rapid IV administration of fentanyl. Muscular rigidity may be associated with reduced pulmonary compliance and/or apnea, laryngospasm, and bronchoconstriction and may be managed by use of assisted or controlled respiration or, if necessary, by IV administration of a neuromuscular blocking agent. Bradycardia may occur following administration of fentanyl and may be controlled with atropine. Delayed chest wall muscle rigidity may develop up to 24 hours after administration or 9 hours after after ending an IV infusion and may persist for hours. Masseter muscle spasm and laryngospasm may also occur. Acute overdosage produces signs of opioid toxicity: circulatory and CNS depression, lethargy, coma, respiratory depression, and decreased GI motility with ileus. Miosis is a variable finding, depending on the particular opioid, co-ingestants, and secondary effects, such as hypoxia. Apnea, hypotension, bradycardia, non-cardiogenic pulmonary edema, seizures, dysrhythmias, and death may occur with severe poisoning. With continued use, tolerance to the pharmacologic and adverse effects of the drug develop, but the rate of development of tolerance exhibits considerable interindividual variation. ANIMAL STUDIES: Fentanyl was not teratogenic in rats at dosages of 10-500 ug/kg daily when administered on days 7-21 of gestation. At an IV dosage of 10-30 ug/kg daily on days 6-18 of gestation in rats, fentanyl was embryotoxic or fetotoxic and slightly increased mean delivery time in animals receiving the highest dosage, but the drug was not teratogenic. At IV doses of 30 ug/kg or subcutaneous doses of 160 ug/kg in rats, fentanyl increased embryonic resorptions. Fentanyl citrate was not mutagenic in the in vitro Ames reverse mutation assay in S. typhimurium or E. coli, or the mouse lymphoma mutagenesis assay, and was not clastogenic in the in vivo mouse micronucleus assay. In veterinary use, overdosage may produce profound respiratory and/or CNS depression in most species. Newborns may be more susceptible to these effects than adult animals. Other toxic effects may include cardiovascular collapse, tremors, reck rigidity, and seizures.Typically, a fentanyl overdose manifests as an extrapolation of its pharmacological side effects. Although the clinical scenarios may vary among patients, one of the main concerns is the level of expression of OIRD. In such cases, oxygen administration and respiratory assistance are a priority. An opioid drug antagonist such as naloxone can help to correct OIRD symptoms. Commonly, repeated doses are necessary since, over time, respiratory depression may overcome the effects of the antagonist drug, particularly with opiates such as fentanyl, in which increased receptor affinity may be present as compared to other opiates. Thus, the therapeutic approach should continue until a normal respiratory rate coincides with appropriate oxygen saturation levels.Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Fentanyl's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hypopolarization and reduced neuronal excitability. |
| Signs and Symptoms | - Irritation may occur.- Contracted or pinpoint pupils (miosis) (may later become dilated), reduced level of consciousness (CNS depression), reduced respiratory function (respiratory depression), reduced blood oxygen content (hypoxia), accumulation of acid in the blood (acidosis), low blood pressure (hypotension), slow heart rate (bradycardia), shock, slowing of muscular movement of the stomach (gastric hypomotility) with intestinal obstruction due to lack of normal muscle function (ileus), accumulation of fluid in the lungs (pulmonary edema), lethargy, coma, and death.- See Ingestion Exposure.More common symptoms are dizziness, light-headedness, or feeling faintdrowsinessnausea or vomitingunusual tiredness or weakness. Less common or rare ones are blurred or double vision or other vision problemsconfusionconstipationconvulsions (seizures)difficult or painful urinationmental depressionshortness of breath, trouble in breathing, tightness in the chest, or wheezingskin rash, hives, or itchingunusual excitement (L1484) |
| Ongoing Test Status | EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of May 1, 2017: http://actor.epa.gov/dashboard/] |
| Effluent Concentrations | Fentanyl was detected in 6% of effluent samples collected from 90 European wastewater treatment plants at <0.5-1.6 ng/L (average 0.1 ng/L, median <0.1 ng/L)samples were collected in 2010(1). Influent and effluent concentrations of fentanyl have been reported as 1.3-1.7 and <0.1-0.5 ng/L, respectively, in wastewater treatment plants(2). |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of fentanyl can be estimated to be 39,600(SRC). According to a classification scheme(2), this estimated Koc value suggests that fentanyl is expected to be immobile. The pKa of fentanyl is 7.3(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). |
| 水環境危害等級（WGK） | 2 |
| RTECS 番号 | UE5550000 |
| 輸送番号（UN） | 1544 |
| 毒性 | LD50 orl-rat: 18 mg/kg JPPMAB 25,929,73 |
| 税関コード | 2933330000 |
| 危険文句（R） | 11-23/25-36/38-39/23/24/25-23/24/25 |
| 危険表示 | F,T |
| 安全措置（S） | 16-24-45-36/37-7 |
| 危険等級 | 6.1(b)Acute Tox. 1 DermalAcute Tox. 1 InhalationAcute Tox. 2 OralSTOT SE 3 |
| 包装等級 | III |
| 貯蔵分類 | 6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials |
| 有害物質データ | 437-38-7(Hazardous Substances Data) |
用途
用途
麻薬性鎮痛薬がん性疼痛などの激しい疼痛時の鎮痛・鎮静
使用
Fentanyl is available in a variety of preparations for parenteral, transdermal and transmucosal (including buccal) administration. Because of high firstpass metabolism (~70%) it is not given orally. It is approximately 80–100 times more potent than morphine in the acute seing, although it is approximately 30–40 times as potent when given chronically (e.g. slowrelease transdermal patches). With transdermal administration, the patch and underlying dermis act as a reservoir, and plasma concentration does not reach steady state until approximately 15h after initial application. Plasma concentration also declines slowly after removal (t1/2 ~15–20 h). Fentanyl is very lipophilic, with a relatively short duration of action. There are several new buccal/transmucosal preparations developed for rapid-onset breakthrough pain. These aim to have a very rapid onset in approximately 10min, although this may not be the case in clinical practice. Fentanyl has a large VD with rapid peripheral tissue uptake, limiting initial hepatic metabolism. This may result in significant variability in plasma concentrations and secondary plasma peaks. It binds to αl-acid glycoprotein and albumin; 40% of the protein-bound fraction is taken up by erythrocytes. The lungs may be important in exerting a first-pass effect on fentanyl (up to 75% of the dose), thus buffering the plasma from high peak drug concentrations.
一般的な説明
When the 4-phenyl substituent of meperidine was replaced with a 4-aniline with a nitrogen connection, the potency increased. This led to the development of the 4-anilidopiperidine series of compounds. Fentanyl (Sublimaze) was the first compound marketed and was found to be almost 500 times more potent than meperidine. The high lipophilicity of fentanyl gave it a quick onset, and the quick metabolism led to a short duration of action. The combination of potency, quick onset, and quick recovery led to the use of fentanyl as an adjunct anesthetic.