Is methoxyflurane a narcotic? A guide to its classification and pharmacology

October 7, 2025 •

4 min read

Multiple studies have shown that methoxyflurane, commonly known by the brand name Penthrox in many countries, is a non-narcotic analgesic. It is not an opioid and does not act on the same receptors as morphine, fentanyl, or heroin.

Quick Summary

Methoxyflurane, a potent non-opioid analgesic and anesthetic, works by modulating the nervous system through various neurotransmitter pathways, not by binding to opioid receptors. The drug is classified differently from narcotics, and its modern use as a self-administered inhaler for acute pain is distinct from its historical use as a general anesthetic.

Key Points

Non-Narcotic Classification: Methoxyflurane is a non-opioid analgesic and anesthetic, fundamentally different from true narcotics like morphine and fentanyl.
Distinct Mechanism: It does not act on opioid receptors but instead modulates neurotransmission by activating GABA receptors to produce pain relief.
Past and Present Uses: While historically used as a general anesthetic, its high-dose toxicity led to its decline. It is now used at low, analgesic doses (e.g., Penthrox) for acute pain in many countries.
US Market Withdrawal: The FDA withdrew methoxyflurane from the US market for safety reasons in 2005, though clinical trials for its reintroduction are underway.
Managed Safety Profile: At controlled analgesic doses, methoxyflurane has a well-documented safety profile, but it requires medical supervision due to potential risks at higher concentrations.
Low Abuse Potential: Because it is not an opioid, methoxyflurane does not carry the same risk of physical dependence and abuse.

What is a narcotic?

To understand why methoxyflurane is not a narcotic, it is crucial to clarify what the term “narcotic” means. The word has evolved and is often used colloquially to refer to any illegal or mind-altering substance. However, in modern pharmacology, a narcotic is synonymous with an opioid. Opioids are a class of drugs derived from or synthesized to mimic the effects of the opium poppy. They act on specific opioid receptors in the brain and spinal cord to produce pain relief, sedation, and a sense of euphoria. Examples of true narcotics include morphine, codeine, fentanyl, and heroin. All narcotics are regulated as controlled substances due to their high potential for abuse and dependence.

Methoxyflurane: A non-opioid analgesic

In contrast to narcotics, methoxyflurane is a fluorinated ether that functions as a volatile anesthetic. It belongs to a different pharmacological class and does not interact with the opioid receptor system. Its mechanism of action is multifaceted and involves interfering with neurotransmission in the central nervous system, particularly by activating the inhibitory GABA receptors. This leads to its analgesic (pain-relieving) and anesthetic effects.

The complex history of methoxyflurane

Methoxyflurane was first introduced in the 1960s as a general anesthetic for surgical procedures. Its potency made it a popular choice, but concerns about dose-dependent nephrotoxicity (kidney damage) and hepatotoxicity (liver damage) at high, anesthetic concentrations led to its gradual discontinuation for general anesthesia. By the 1980s, safer alternatives had replaced it in operating rooms.

However, methoxyflurane found a new purpose at much lower analgesic doses, where the risk of organ toxicity was minimized. This led to its "reincarnation" as a self-administered inhaled analgesic, most notably as the "green whistle" (Penthrox) in Australia and other countries. It is widely used in emergency and pre-hospital settings for acute, moderate-to-severe trauma pain.

Key differences between methoxyflurane and narcotics


Characteristic	Methoxyflurane (Non-Narcotic Analgesic)	Narcotic (Opioid Analgesic)
Drug Classification	Volatile Anesthetic/Analgesic	Opioid Analgesic/Controlled Substance
Mechanism of Action	Modulates neuronal activity via GABA and other neurotransmitter systems	Binds to and activates specific opioid receptors
Receptor Targets	GABA receptors, glycine receptors, and more	Mu, kappa, and delta opioid receptors
Abuse Potential	Non-addictive and not associated with typical opioid abuse	High potential for physical dependence and addiction
Side Effects	Dizziness, headache, nausea, potential nephrotoxicity at high doses	Respiratory depression, sedation, constipation, nausea, dependence
Legal Status (US)	Not available for general medical use (withdrawn by FDA)	Highly regulated under the Controlled Substances Act (Schedules I-V)

Why is methoxyflurane not available everywhere?

The fact that methoxyflurane is not a narcotic does not mean it is without risks. The FDA withdrew it from the US market in 2005 due to past evidence of severe nephrotoxicity and hepatotoxicity associated with anesthetic doses. Even though the risk is significantly lower at analgesic doses, the FDA has maintained a cautious approach.

However, in recent years, the FDA has lifted its clinical hold, allowing for phase 3 trials to evaluate a low-dose, inhaler-based formulation, potentially paving the way for its reintroduction to the US market. Meanwhile, it continues to be a standard analgesic in many countries, including Australia, New Zealand, and parts of Europe, used safely under controlled supervision for emergency pain relief.

Conclusion

To conclude, methoxyflurane is definitively not a narcotic. It is a non-opioid, non-addictive medication that works through a different pharmacological mechanism to provide potent analgesia. While its history as an anesthetic was complicated by organ toxicity, its modern use at low, controlled doses as an inhaled analgesic has demonstrated effectiveness and a manageable safety profile in many parts of the world. Its classification as a volatile anesthetic and its mechanism of action fundamentally distinguish it from true narcotics and make it a valuable alternative for acute pain management outside the US. The eventual outcome of its reevaluation by the FDA in the US will determine its future availability in North America.

Frequently asked questions

How does methoxyflurane provide pain relief if it's not a narcotic? Methoxyflurane relieves pain by modulating neurotransmission in the brain and spinal cord, acting on GABA and other receptors to disrupt nerve signaling, rather than binding to opioid receptors like narcotics.
Is methoxyflurane addictive? No, methoxyflurane is not addictive. Unlike opioids (narcotics), it does not produce the same potential for physical dependence or addiction.
What is Penthrox? Penthrox is the brand name for a self-administered inhaler device that delivers low-dose methoxyflurane for acute pain relief in many countries, especially in emergency settings.
Why was methoxyflurane removed from the market in the US? The FDA withdrew methoxyflurane from the US market in 2005 due to concerns about dose-dependent nephrotoxicity and hepatotoxicity when used at anesthetic doses.
Is it safe to use methoxyflurane now? When used at the low analgesic doses in a supervised setting, such as with the Penthrox inhaler, the risk of serious side effects like kidney damage is significantly lower compared to anesthetic doses. Proper medical supervision is essential.
Is methoxyflurane a controlled substance? The classification varies by country. In the US, it is not a controlled substance, but it is not available for general medical use. In countries where it is used, it is typically a prescription-only medication.
How does methoxyflurane differ from nitrous oxide? Both are inhaled analgesics, but methoxyflurane is a more potent analgesic and is administered via a single-patient inhaler, offering an alternative that is lighter and easier to transport than nitrous oxide tanks.

Frequently Asked Questions

No, methoxyflurane is not an opioid. Opioids are a class of drugs that bind to opioid receptors in the brain, while methoxyflurane acts on different neurochemical pathways, primarily by activating GABA receptors to achieve analgesia.

Anesthetics cause a loss of sensation, with some (like methoxyflurane) producing pain relief (analgesia). Narcotics are a type of opioid drug that primarily relieve pain and produce a state of stupor or euphoria by acting on opioid receptors.

The brand name Penthrox, which is a methoxyflurane inhaler, is commonly known as the 'green whistle' because of the distinct green color of the handheld, whistle-shaped device used for self-administration.

No, methoxyflurane is not considered addictive in the same way as narcotics (opioids). It is not associated with the same risk of physical dependence and addiction that characterizes opioids.

No, methoxyflurane was withdrawn from the US market by the FDA in 2005 due to concerns over toxicity at anesthetic doses. While it is widely used in other countries for pain relief, its status in the US is pending further review and clinical trials.

At the low doses used for analgesia, common side effects include dizziness, headache, and sleepiness. More serious side effects, such as kidney or liver problems, are associated with historical use at much higher anesthetic doses.

It is primarily used for emergency relief of acute, moderate-to-severe pain, particularly from trauma. It is also used for short procedures where pain relief is required, such as changing dressings or repositioning patients.