Fentanyl

N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide

Overview

Fentanyl belongs to Opioids.

Key safety note: Fentanyl has an extremely narrow margin between an effective and a lethal dose, and respiratory depression is the principal cause of death.^[5]^[6]

Effects

Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.

At therapeutic (analgesic) doses: rapid, strong pain relief with drowsiness, nausea, constipation and pinpoint pupils.
At higher or recreational doses: intense opioid euphoria, warmth and relaxation, but with pronounced sedation, itching, slowed breathing and a high risk of respiratory arrest.
Onset is rapid (IV within minutes, insufflated or oral roughly 15–30 minutes) and the subjective effects are relatively short (about 1–4 hours), which can prompt redosing and further raise overdose risk.

Dosing & duration

Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Medical: intravenous, epidural or intrathecal. Transdermal patch. Transmucosal lozenge, buccal film or nasal spray. Non-medical use is also by insufflation, smoking or injection.. Fentanyl is active in the microgram (µg) range, roughly a hundredth of the milligram doses of morphine, so there is no safe way to measure a recreational dose of illicitly manufactured fentanyl by eye. The figures below are reference ranges for relatively pure, pharmaceutical-grade fentanyl and are NOT a recommendation or a 'safe' dose. Illicit powders and counterfeit pills are unevenly mixed, so the same visible amount can range from inactive to lethal. There is no safe margin for error: never use alone, keep naloxone (multiple doses) on hand, and use fentanyl test strips to check other drugs.

Dose ranges

Threshold

5–10 µg

Light

10–25 µg

Common

25–50 µg

Strong

50–75 µg

Heavy

75 µg +

Duration

onset

IV within minutes, insufflated or oral ≈15–30 minutes

total

≈1–4 hours (transdermal patches last far longer)

after effects

Sedation and constipation. Tolerance and physical dependence with repeated use

Chemical & Physical Properties

Formula	C22H28N2O
Molar mass	336.47 g/mol
State	Solid
Melting point	85.2 °C
Boiling point	Not reported
Density	Not reported
Vapor pressure	4.43×10⁻⁹ mmHg at 25 °C (extrapolated)
pKa	8.43
LogP	4.05
Solubility	0.74mg/mL, In water, 200 mg/L at 25 °C, 2.40×10⁻² g/L
Refractive index	Not reported

Identifiers & Synonyms

CAS	437-38-7
CAS (enantiomer)
PubChem CID	3345
InChIKey	PJMPHNIQZUBGLI-UHFFFAOYSA-N
InChI	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
SMILES	CCC(=O)N(C1CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3

Synonyms

Fentanil
Sublimaze
Duragesic
N-(1-phenethylpiperidin-4-yl)-N-phenylpropanamide
Fenty

Pharmacodynamics & Biochemistry

Fentanyl is a synthetic phenylpiperidine opioid and a potent, selective full agonist at the μ-opioid receptor (MOR): roughly 50–100 times more potent than morphine. It is highly lipophilic, so it crosses the blood–brain barrier rapidly to give a fast onset. This combination of high potency and speed underlies both its clinical usefulness and its lethality. MOR is a Gi/o-coupled receptor: activation inhibits adenylyl cyclase (lowering cAMP), opens G-protein-gated inwardly rectifying K⁺ (GIRK) channels and closes voltage-gated Ca²⁺ channels, hyperpolarising neurons and reducing neurotransmitter release. This produces analgesia, sedation and euphoria, while μ-agonism in the brainstem respiratory centres depresses the drive to breathe, the mechanism of fatal overdose, and peripheral MOR activation causes miosis (pinpoint pupils) and constipation. Affinity at the κ- and δ-opioid receptors is roughly a thousand-fold lower than at MOR, so fentanyl's effects are essentially μ-mediated. A distinctive adverse effect is fentanyl-induced muscle and chest-wall rigidity ('wooden chest' syndrome), which can impair ventilation independently of central respiratory depression and responds poorly to naloxone. Fentanyl is metabolised mainly by hepatic CYP3A4 to the essentially inactive metabolite norfentanyl, so CYP3A4 inhibitors and inducers markedly change exposure. After an IV dose the effect is brief because the drug redistributes out of the brain, but transdermal patches and repeated dosing form a depot that gives a long apparent half-life.

Biological targets

Binding & functional measurements

Target	Measurement	Species
μ-opioid receptor	Ki 1.3 nM	Human
κ-opioid receptor	Ki 85 ± 19 nM	Human
δ-opioid receptor	Ki 153 ± 38 nM	Human
δ-opioid receptor	Ki 74 ± 3.5 nM	Guinea pig
κ-opioid receptor	Ki 151 ± 5.2 nM	Guinea pig
μ-opioid receptor	Ki 1.0 ± 0.10 nM	Guinea pig
μ-opioid receptor	EC50 110 ± 30 nM Emax 62 ± 3%	Human

Pharmacokinetics

Bioavailability	IV 100%, transdermal ≈92%, oral transmucosal ≈50%
T_max	IV: ~minutes, transdermal patch: 12–24 h
Half-life	IV ≈3–7 h, transdermal apparent ≈20–27 h (depot)
V_d	≈4–6 L/kg
Protein binding	≈80–85%
Metabolism	Hepatic CYP3A4 to inactive norfentanyl
Excretion	Primarily renal (<10% unchanged)

Toxicology & Safety

Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

3.1 mg/kg (mouse, i.v.)

Fentanyl has an extremely narrow margin between an effective and a lethal dose, and respiratory depression is the principal cause of death. Because it is active in the microgram range, illicitly manufactured fentanyl and its analogues cannot be measured or 'eyeballed' safely: uneven mixing into powders and counterfeit pills means a single pill or line can be a fatal dose. It is the leading driver of opioid-overdose deaths in North America, and the illicit supply is increasingly adulterated with xylazine ('tranq', which naloxone does not reverse) and with other potent analogues. Naloxone reverses fentanyl, but because fentanyl is so potent and can outlast a single dose, repeat naloxone dosing is often needed. Fentanyl also causes chest-wall/muscle rigidity ('wooden chest') that can impair breathing, and, like all opioids, produces tolerance and physical dependence. Fentanyl test strips can detect its presence in other drugs.^[5]^[6]

Legal Status

Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.

US: Schedule II. UK: Class A. DE: BtMG Anlage III

Interactions & Contraindications

Drug interactions

Benzodiazepines, Alcohol Life-threatening respiratory depression (FDA boxed warning).^[5]^[4]

CYP3A4 inhibitors (ritonavir, azole antifungals, macrolides, grapefruit) Ritonavir, ketoconazole or clarithromycin increase and prolong the effect.^[4]^[5]

CYP3A4 inducers (rifampicin, carbamazepine) Rifampicin or carbamazepine reduce efficacy and risk withdrawal.^[4]^[5]

MAOIs, Other serotonergic drugs Serotonin syndrome.^[5]^[4]

Contraindications

Significant respiratory depression or acute severe asthma including acute or severe bronchial asthma in unmonitored settings.^[5]^[4]

Paralytic ileus or gastrointestinal obstruction^[4]

Opioid-naive (no tolerance) transdermal or long-acting forms.^[5]^[4]

Usage & Context

Widely used in medicine as a potent analgesic and anaesthetic adjunct: intravenously in surgery and intensive care, as transdermal patches for chronic severe pain, and as lozenges, buccal films or nasal sprays for breakthrough cancer pain.
A major illicit drug: illicitly manufactured fentanyl and its analogues are pressed into counterfeit pills or mixed into heroin and other powders, frequently without the user's knowledge.
The dominant driver of the North American opioid-overdose crisis, and increasingly detected in the illicit drug supply worldwide.

Sources & Evidence

Further Information

More in this subclass