3-메틸펜타닐; 프로판아마이드, N-(3-메틸-1-(2-페닐에틸)-4-피페리디닐)-N-페닐-

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.

Three fatal poisoning cases due to 3-methylfentanyl are described. In each case, the death was accidental and occurred after injection of the opioid combined with amphetamine, heroin, or other drugs. The victims' ages, ranging from 30 to 41 years, were higher than those typically found in heroin poisonings in Finland. The blood concentrations of cis-3-methylfentanyl, measured here for the first time by a specific tandem mass spectrometric method, ranged from 0.3 to 0.9 ug/L (mean 0.5 ug/L). These values are significantly lower than the levels reported for alpha-methylfentanyl and fentanyl in fatal poisonings. Repeated seizures of fentanyl and its analogs have been reported in Europe close to the Russian border.

An exceptional epidemic of poisonings due to the highly potent opioid designer drug 3-methylfentanyl (TMF) was revealed among Estonian drug users in 2005-2006 by post-mortem forensic toxicology. Quantitative analysis of cis-TMF, trans-TMF, and fentanyl was performed by liquid chromatography-tandem mass spectrometry. Comprehensive toxicological analysis was performed using a multi-technique approach. The number of TMF-related fatal accidental poisonings identified was 46 and 71 for 2005 and 2006, respectively. The proportion of male victims was 91.5% and the mean age of all victims was 26 years at death. TMF was used predominantly by intravenous injection. There was no significant difference in the blood concentrations of cis-TMF and trans-TMF between pure TMF poisonings and mixed TMF poisonings. The mean combined concentration of TMF stereoisomers among pure TMF cases (1.9 ug/L) was more than ten times lower than the mean fentanyl concentration in fentanyl-related fatalities. Concomitant use of other drugs involved alcohol, amphetamines, benzodiazepines, and cannabis, but very rarely other opioids.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 65,000(SRC), determined from a structure estimation method(2), indicates that 3-methylfentanyl is expected to be immobile in soil(SRC). The estimated pKa of 3-methylfentanyl is 9.08(3), indicating that this compound will exist almost entirely 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). Volatilization of the cation from moist soil is not expected because cations do not volatilize(SRC). 3-Methylfentanyl is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.9X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 65,000(SRC), determined from a structure estimation method(2), indicates that 3-methylfentanyl is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 9.08(3) indicates 3-methylfentanyl will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). 3-Methylfentanyl 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(5), an estimated BCF of 320(SRC), from an estimated log Kow of 4.31(2) 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), 3-methylfentanyl, which has an estimated vapor pressure of 2.9X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase. Particulate-phase 3-methylfentanyl may be removed from the air by wet and dry deposition(SRC). 3-Methylfentanyl contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: 3-Methylfentanil (TMF) is a Schedule I controlled substance. The opioid TMF is a designer drug of the fentanyl type with high potency and abuse potential. HUMAN STUDIES: An exceptional epidemic of poisonings due to TMF was revealed among Estonian drug users in 2005-2006 by post-mortem forensic toxicology. TMF was used predominantly by intravenous injection. Concomitant use of other drugs involved alcohol, amphetamines, benzodiazepines, and cannabis, but very rarely other opioids. More recently, reports indicate that both fentanyl and TMF have been marketed as a replacement for heroin in European countries. ANIMAL STUDIES: Intravenous administration of (+)-cis-TMF (50 ug/kg) to rats produced a pronounced catalepsy.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 3-methylfentanyl can be estimated to be 65,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that 3-methylfentanyl is expected to be immobile in soil. The estimated pKa of 3-methylfentanyl is 9.08(3), indicating that this compound will exist almost entirely in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/CASE REPORTS/ Three fatal poisoning cases due to 3-methylfentanyl are described. In each case, the death was accidental and occurred after injection of the opioid combined with amphetamine, heroin, or other drugs. The victims' ages, ranging from 30 to 41 years, were higher than those typically found in heroin poisonings in Finland. The blood concentrations of cis-3-methylfentanyl, measured here for the first time by a specific tandem mass spectrometric method, ranged from 0.3 to 0.9 ug/L (mean 0.5 ug/L). These values are significantly lower than the levels reported for alpha-methylfentanyl and fentanyl in fatal poisonings. Repeated seizures of fentanyl and its analogs have been reported in Europe close to the Russian border.

/CASE REPORTS/ An exceptional epidemic of poisonings due to the highly potent opioid designer drug 3-methylfentanyl (TMF) was revealed among Estonian drug users in 2005-2006 by post-mortem forensic toxicology. Quantitative analysis of cis-TMF, trans-TMF, and fentanyl was performed by liquid chromatography-tandem mass spectrometry. Comprehensive toxicological analysis was performed using a multi-technique approach. The number of TMF-related fatal accidental poisonings identified was 46 and 71 for 2005 and 2006, respectively. The proportion of male victims was 91.5% and the mean age of all victims was 26 years at death. TMF was used predominantly by intravenous injection. There was no significant difference in the blood concentrations of cis-TMF and trans-TMF between pure TMF poisonings and mixed TMF poisonings. The mean combined concentration of TMF stereoisomers among pure TMF cases (1.9 ug/L) was more than ten times lower than the mean fentanyl concentration in fentanyl-related fatalities. Concomitant use of other drugs involved alcohol, amphetamines, benzodiazepines, and cannabis, but very rarely other opioids.

/OTHER TOXICITY INFORMATION/ Fentanyl is a synthetic opioid analgesic historically used as a pain reliever and an anesthetic. Recent concerns have arisen around the illicit use of fentanyl and its analogs in a number of European countries, linked to their high potency and associated risk of fatal overdose. Evidence has been emerging from Estonia for over a decade of entrenched patterns of fentanyl use, including injection of the drug and hundreds of overdose deaths. More recently, reports indicate that both fentanyl and 3-methylfentanyl (TMF) have been marketed as a replacement for heroin in European countries (e.g. Bulgaria, Slovakia) affected by heroin shortages. In addition, Germany, Finland and the United Kingdom, reported new outbreaks of fentanyl-related deaths. This combination of increasing mortality data alongside law enforcement intelligence suggesting both diversion and illicit production of fentanyls, prompted wider investigation using a targeted multi-source data collection exercise and analysis. This identified that in the European context, fentanyls are 'low use but high risk/harm' substances. Evidence shows that Estonia stands out as having an endemic problem, while the use of fentanyls in other European countries appears to be geographically localized. Developments in illicit supply of fentanyls reflect the complexity of Europe's contemporary drug market: manifesting illicit production and use, the diversion and misuse of medicines, and the online sale of non-controlled new psychoactive substances. Likewise effective and integrated responses will need to address fentanyl production, diversion as well as ensuring the availability of harm reduction measures to users.

3-Methylfentanyl's production and use as an illegal drug(1) will result in its release to the environment through various waste streams(SRC). It is classified as a Schedule I illegal narcotic(1). There are no registered uses for 3-methylfentanyl, an opiate(2).

An estimated BCF of 320 was calculated in fish for 3-methylfentanyl(SRC), using an estimated log Kow of 4.31(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is high.

An estimated pKa of 9.08(1) indicates 3-methylfentanyl will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces is not expected to be an important fate process(SRC). 3-Methylfentanyl is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.9X10-9 mm Hg(SRC), determined from a fragment constant method(2).

3-Methylfentanyl is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). 3-Methylfentanyl contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Occupational exposure and general population exposure should be low or non-existent since 3-methylfentanyl is no longer produced or used legally in the US. Exposure to 3-methylfentanyl is limited to those producing and using it as an illicit drug. (SRC)

3-Methylfentanyl's production and use as an illegal drug will result in its release to the environment through various waste streams. It is classified as a Schedule I illegal narcotic. There are no registered uses for 3-methylfentanyl, an opiate. If released to air, an estimated vapor pressure of 2.9X10-9 mm Hg at 25 °C indicates 3-methylfentanyl will exist solely in the particulate phase in the atmosphere. Particulate-phase 3-methylfentanyl will be removed from the atmosphere by wet and dry deposition. 3-Methylfentanyl contains chromophores that absorb at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, 3-methylfentanyl is expected to have no mobility based upon an estimated Koc of 65,000. The estimated pKa of 3-methylfentanyl is 9.08, indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. 3-Methylfentanyl is not expected to volatilize from dry soil surfaces based upon its estimated vapor pressure. Biodegradation data in soil or water were not available. If released into water, 3-methylfentanyl is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated pKa. An estimated BCF of 320 suggests the potential for bioconcentration in aquatic organisms is high. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure and general population exposure should be low or non-existent since 3-methylfentanyl is no longer produced or used legally in the US. Exposure to 3-methylfentanyl is limited to those producing and using it as an illicit drug. (SRC)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat coma, seizures, hypotension, and noncardiogenic pulmonary edema if they occur. /Opiates and opioids/

For more Antidote and Emergency Treatment (Complete) data for 3-Methylfentanil (7 total), please visit the HSDB record page.

Schedule I 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 listed in another schedule, any of the following opiates, including their 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 (for purposes of paragraph (b)(34) only, the term isomer includes the optical and geometric isomers). 3-Methylfentanyl (N-[3-methyl-1-(2-phenylethyl)-4-piperidyl]-N-phenylpropanamide) (DEA Code Number: 9813) is included on this list.

3-Methylfentanyl (DEA Code Number: 9813) is a Schedule I controlled substance.

Schedule I Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has no currently accepted medical use in treatment in the United States; and (C) There is a lack of accepted safety for use of the drug or other substance under medical supervision.

Analgesics

Fentanyl is a synthetic opioid analgesic historically used as a pain reliever and an anaesthetic. Recent concerns have arisen around the illicit use of fentanyl and its analogues in a number of European countries, linked to their high potency and associated risk of fatal overdose. Evidence has been emerging from Estonia for over a decade of entrenched patterns of fentanyl use, including injection of the drug and hundreds of overdose deaths. More recently, reports indicate that both fentanyl and 3-methylfentanyl (TMF) have been marketed as a replacement for heroin in European countries (e.g. Bulgaria, Slovakia) affected by heroin shortages. In addition, Germany, Finland and the United Kingdom, reported new outbreaks of fentanyl-related deaths. This combination of increasing mortality data alongside law enforcement intelligence suggesting both diversion and illicit production of fentanyls, prompted wider investigation using a targeted multi-source data collection exercise and analysis. This identified that in the European context, fentanyls are 'low use but high risk/harm' substances. Evidence shows that Estonia stands out as having an endemic problem, while the use of fentanyls in other European countries appears to be geographically localised. Developments in illicit supply of fentanyls reflect the complexity of Europe's contemporary drug market: manifesting illicit production and use, the diversion and misuse of medicines, and the online sale of non-controlled new psychoactive substances. Likewise effective and integrated responses will need to address fentanyl production, diversion as well as ensuring the availability of harm reduction measures to users.