3-Methylfentanyl, also known as 3-MF or fentanyl, is an opioid analgesic classified as an analog of fentanyl. This potent opioid is estimated to be one of the most powerful available, with its strength varying considerably depending on the specific isomer used. The cis isomers are recognized as the more potent variants, with 3-methyl fentanyl estimated to be between 400 and 6000 times more potent than morphine.

IUPAC name
CAS Number42045-86-3 
PubChem CID61996
CompTox Dashboard (EPA)DTXSID30962228
Chemical and physical data
Molar mass350.506 g·mol−1

Overview and history

The discovery of 3-methyl fentanyl dates back to 1974, and it emerged as an alternative to the clandestinely produced fentanyl analog known as α-methyl fentanyl. However, it became evident that 3-methylfentanyl was significantly more potent than α-methylfentanyl, rendering it correspondingly more hazardous.
The chemical structure of fentanyl has served as a foundation in modern chemistry for identifying and naming numerous new fentanyl analogs, often referred to as catalogs.
Although 3-methyl fentanyl was briefly available on the black market between 1984 and 1985, its remarkable potency made it an attractive choice for illicit drug manufacturers. Racemic 3-MF, in particular, is 10–15 times more potent than fentanyl, enabling the production of significantly larger quantities of diluted product for street sales with the same amount of effort as producing fentanyl itself. For instance, a single gram of 3-methyl fentanyl could yield several thousand dosage units for sale. As a result, 3-MF has resurfaced multiple times in various locations worldwide.
Estonia is the only country where significant chemical abuse has been reported, with over 200 deaths annually and over 10,000 addicts. In Estonia, a dose of 3-MF costs 10 €, and other opiates have generally not been available since the end of the 2000s. From 2005 to 2013, approximately 1,100 deaths related to fentanyl and 3-MF abuse were documented in Estonia, in contrast to about 450 deaths in Sweden, Germany, the UK, Finland, and Greece combined over the same period.
Although more potent opioid analogs exist, such as carfentanil and ohmefentanyl, they are notably more challenging to manufacture than 3-methylfentanyl. Since 2016, fentanyl seizures in Estonia have predominantly contained carfentanil or cyclopropyl fentanyl.
3-Methylfentanyl produces effects similar to fentanyl but is considerably more potent due to its increased binding affinity for the target site. Because fentanyl is already highly potent, 3-methyl fentanyl poses an extreme danger when used recreationally and has resulted in numerous fatalities among recreational opioid users. The side effects of fentanyl analogs mirror those of fentanyl itself and may include itching, nausea, and potentially life-threatening respiratory depression. Fentanyl analogs have caused hundreds of fatalities across Europe and the former Soviet republics since their resurgence in use commenced in Estonia in the early 2000s, with novel derivatives continuing to emerge.

Use as chemical weapon

3-Methylfentanyl was also identified by the media as the substance used in the anesthetic “gas” Kolokol-1, delivered as an aerosol during the Moscow theater hostage crisis in 2002, where many hostages succumbed to accidental overdoses. It was later determined that 3-methylfentanyl was not the primary agent used. The opiate antidote naloxone was administered to treat the victims of the crisis. Nevertheless, due to various factors, including the hostages’ confinement, lack of food, water, or sleep, or the novel nature of the yet-unconfirmed compound employed, acute symptoms persisted, resulting in numerous fatalities despite naloxone administration.


Several methods for the synthesis of 3-methyl fentanyl have been documented. The Serbian chemical society posted one of the most recent methods in 2004. Another method involves constructing N-Benzyl-3-methyl-4-piperidone through a two-stage Michael reaction, followed by a Dieckmann cyclization, as is customary for such syntheses.


  • What is 3-methylfentanyl?
  • 3-Methylfentanyl is a synthetic opioid analgesic that belongs to the fentanyl family of drugs. It is known for its exceptional potency, estimated to be significantly stronger than morphine.
  • When was 3-methylfentanyl first discovered?
  • 3-Methylfentanyl was first discovered in 1974.
  • How potent is 3-methylfentanyl compared to morphine?
  • The potency of 3-methylfentanyl is estimated to be between 400 and 6000 times stronger than morphine, depending on the specific isomer used.
  • What are the effects of 3-methylfentanyl?
  • Like other opioids, 3-methylfentanyl produces analgesic effects. However, its extraordinary potency can lead to severe respiratory depression, itching, nausea, and even death, especially when used recreationally.
  • Is 3-methylfentanyl associated with adverse health effects?
  • Yes, using 3-Methylfentanyl and similar potent opioids is associated with severe health risks, including respiratory depression and overdose. These substances have led to numerous deaths, primarily among recreational opioid users.
  • Where has 3-methylfentanyl been a significant issue?
  • Estonia has experienced significant problems with 3-methylfentanyl abuse, resulting in numerous deaths. The substance is particularly prevalent in Estonia, where other opiates have become scarce.
  • Are there even more potent opioids than 3-methylfentanyl?
  • Some opioids, such as carfentanil and ohmefentanyl, are even more potent than 3-methylfentanyl. However, these substances are more challenging to manufacture.
  • Has 3-methylfentanyl been associated with criminal incidents?
  • In the Moscow theater hostage crisis in 2002, 3-methylfentanyl was initially reported to be used as an aerosol, contributing to accidental overdoses. It was later ruled out as the primary agent used.
  • How is 3-methylfentanyl synthesized?
  • Several methods for synthesizing 3-Methylfentanyl have been published in the scientific literature. Researchers have explored different approaches to producing this powerful opioid.
  • Are there any known scientific studies related to 3-methylfentanyl?
  • Numerous scientific studies have been conducted on 3-methylfentanyl, exploring its pharmacological properties, synthesis methods, and health effects. These studies have contributed to our understanding of this substance and its dangers.


  1. In a Journal of Forensic Sciences article from 1988, Henderson GL explored the world of designer drugs, shedding light on their past history and what the future might hold.
  2. Back in May 1981, a study by Jin WQ and colleagues delved into the synthesis and the relationship between analgesic activity and receptor affinity for derivatives of 3-methyl fentanyl, adding valuable insights into its properties.
  3. Wang ZX and his team published research in 1993 regarding stereoisomers of 3-methylfentanyl. This research touched upon their synthesis, absolute configuration, and analgesic activity.
  4. The early ’70s saw significant pharmacological research. In October 1974, Van Bever WF, Niemegeers CJ, and Janssen PA conducted studies on the synthesis and pharmacology of diastereoisomers of N-(3-methyl-1-(2-phenylethyl)-4-piperidyl)-N-phenylpropanamide, shedding light on the substance’s properties.
  5. A 1981 report by Ayres WA and others tackled the issue of counterfeit drugs. It specifically highlighted cases involving three-methyl and alpha-methyl fentanyl, which were being sold as ‘China White’.
  6. In February 1991, an outbreak of designer drug-related deaths in Pennsylvania was discussed in the Journal of the American Medical Association (JAMA)[6]. Hibbs J, Perper J, and Winek CL contributed to the understanding of the situation.
  7. Estonia faced an epidemic of fatal 3-methylfentanyl poisoning between 2005 and 2013, as reported in the International Journal of Legal Medicine in September 2008. Ojanperä I, Gergov M, Liiv M, Riikoja A, and Vuori E documented the alarming situation.
  8. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) has been closely monitoring the drug market in Estonia, tracking the impact and distribution of these substances.
  9. In July 2015, Mounteney J, Giraudon I, Denissov G, and Griffiths P explored the rise of fentanyls in Europe. They discussed the significant increase in the use of these potent substances.
  10. Huang ZM and his team conducted research on the analgesic activity and toxicity of potent analgesics, including ohmefentanyl and mefentanyl, back in September 1984.
  11. Anneli Uusküla’s scoping review, published in 2020, delved into the fentanyl epidemic in Estonia, examining the factors contributing to its evolution and offering insights for a comprehensive public health response.
  12. The Moscow theater crisis in 2002 involved the release of an unknown chemical agent as an aerosol. Despite naloxone administration, the crisis resulted in fatalities, leading to further investigation into the substances used.
  13. In 2004, Ivanović M and his team conducted a study on the synthesis and preliminary pharmacological evaluation of racemic cis and trans 3-alkylfentanyl analogues. This research provided insights into the properties of these substances.

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