Oxymorphone

4,5α-epoxy-3,14-dihydroxy-17-methylmorphinan-6-one

Overview

Oxymorphone belongs to Opioids.

Key safety note: Oxymorphone is a high-potency strong opioid (≈10× morphine by injection), and its central danger is dose-dependent respiratory depression, the usual mechanism of opioid death, greatest in opioid-naïve people, at higher doses, and above all when combined with other CNS depressants (benzodiazepines, alcohol, gabapentinoids, other opioids), a combination that carries an FDA boxed warning.[5][6][3]
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.
  • Pain relief with a warm, relaxed calm and, especially at higher or injected doses, marked euphoria. Drowsiness and clouded thinking.
  • Physical signs: pinpoint pupils, slowed breathing, itch, nausea/vomiting and constipation.
  • With regular use: tolerance to the euphoria and analgesia (but not to constipation), physical dependence, and a flu-like opioid withdrawal on stopping.
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.

Oral (immediate-release, extended-release Opana ER now withdrawn) and by injection (IM/IV/subcutaneous): clinician-prescribed and titrated. Figures below are clinical context, NOT a recreational guide.. Oxymorphone is a high-potency prescription opioid. Dosing is individualised and titrated to effect and tolerance, with very different doses in opioid-naïve versus opioid-tolerant patients. There is no safe recreational dose. It is roughly 10× as potent as morphine by injection and about 3× as an oral dose, so the margin between a euphoric and a fatal dose is small, and any other CNS depressant multiplies the danger. Extended-release tablets had to be swallowed whole. Crushing, dissolving and injecting them was a frequent cause of overdose and, through shared needles, of HIV/hepatitis-C transmission. Have naloxone available. Never use alone.

Dose ranges

Oral IR (opioid-naïve adult, clinical)

≈5–10 mg every 4–6 h, titrated

Parenteral (IM/SC, clinical)

≈1–1.5 mg every 4–6 h

Equianalgesic reference

Parenteral oxymorphone ≈10× morphine, oral oxymorphone ≈3× oral morphine

Duration

onset

Oral IR ≈30 min, IV ≈5–10 min

total

Analgesia ≈4–6 h (oral IR), ER formerly ≈12 h

after effects

Sedation/constipation may persist. Withdrawal on cessation after regular use

Chemical & Physical Properties
FormulaC17H19NO4
Molar mass301.34 g/mol
StateSolid
Melting point248–249 °C
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKa8.17
LogP0.83
Solubility24000 mg/L, Soluble in boiling acetone and chloroform. Readily soluble in aqueous alkalies. Moderately soluble in boiling ethanol. Sparingly soluble in benzene, 2.56×10¹ g/L
Refractive indexNot reported
Identifiers & Synonyms
CAS76-41-5
CAS (enantiomer)
PubChem CID5284604
InChIKeyUQCNKQCJZOAFTQ-ISWURRPUSA-N
InChIInChI=1S/C17H19NO4/c1-18-7-6-16-13-9-2-3-10(19)14(13)22-15(16)11(20)4-5-17(16,21)12(18)8-9/h2-3,12,15,19,21H,4-8H2,1H3/t12-,15+,16+,17-/m1/s1
SMILESCN1CC[C@]23[C@@H]4C(=O)CC[C@]2([C@H]1CC5=C3C(=C(C=C5)O)O4)O

Synonyms

  • Opana
  • Numorphan
  • Oxymorphone
Pharmacodynamics & Biochemistry

Oxymorphone is a semi-synthetic μ-opioid receptor (MOR) agonist of the morphinan class, made from thebaine/oripavine. Structurally it is the 3-hydroxy (3-O-desmethyl) analogue of oxycodone, which is why oxycodone is partly converted to oxymorphone in the body. Like other opioid agonists it acts through Gi/Go signalling to reduce neuronal excitability and neurotransmitter release along pain pathways, producing analgesia together with euphoria, sedation, pinpoint pupils, cough suppression, constipation and, the dangerous effect, depression of the brainstem respiratory drive (reversible by naloxone). It is a high-affinity, MOR-selective full agonist: radioligand-binding Kᵢ values are ≈0.78 nM at μ, with much weaker binding at the δ (≈50 nM) and κ (≈137 nM) receptors (MOR:DOR:KOR ≈ 1:64:176). This makes it markedly more potent than morphine, roughly 10× by injection and about 3× as an oral dose, although its oral bioavailability is low (≈10%). Unlike oxycodone, oxymorphone is cleared largely independently of the cytochrome-P450 system: it is metabolised mainly by hepatic glucuronidation to oxymorphone-3-glucuronide, with minor reduction to 6-hydroxy-oxymorphone and N-demethylation to noroxymorphone, so CYP2D6/CYP3A4 drug interactions matter less than for oxycodone. Its extended-release tablet (Opana ER) became a notable public-health problem: after a 2012 'crush-resistant' reformulation, misuse shifted from snorting to injection, and in 2017 the FDA for the first time asked a manufacturer to pull a marketed opioid, citing injection-related HIV and hepatitis-C outbreaks and a serious blood disorder (thrombotic microangiopathy).

Biological targets

  • MOR

Binding & functional measurements

TargetMeasurementSpecies
δ-opioid receptorEC50 259 ± 33 nM
Emax 87 ± 40%		Human
δ-opioid receptorKi 81 ± 5.5 nMRat
κ-opioid receptorKi 62 ± 1.2 nMGuinea pig
κ-opioid receptorEC50 463 ± 116 nM
Emax 48 ± 11%		Human
μ-opioid receptorEC50 4.4 ± 0.76 nM
Emax 98 ± 1%		Human
μ-opioid receptorKi 0.41 nMHuman
μ-opioid receptorKi 0.97 ± 0.05 nMRat
Pharmacokinetics
BioavailabilityOral ≈10%
TmaxNot reported
Half-life≈7–9 h
VdNot reported
Protein binding≈10%
MetabolismHepatic glucuronidation. CYP-independent
ExcretionRenal
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.

Not reported

Oxymorphone is a high-potency strong opioid (≈10× morphine by injection), and its central danger is dose-dependent respiratory depression, the usual mechanism of opioid death, greatest in opioid-naïve people, at higher doses, and above all when combined with other CNS depressants (benzodiazepines, alcohol, gabapentinoids, other opioids), a combination that carries an FDA boxed warning. Overdose (pinpoint pupils, unconsciousness, slow or absent breathing) is a medical emergency reversible with naloxone. It has a high abuse and dependence potential: tolerance and physical dependence develop with repeated use, and abrupt cessation causes an opioid withdrawal syndrome. The extended-release tablet (Opana ER) was especially dangerous when misused: crushing and injecting it delivered the whole dose at once and, through shared needles, drove outbreaks of HIV and hepatitis C plus cases of thrombotic microangiopathy, which led the FDA to have it withdrawn from the US market in 2017. Alcohol can trigger dose-dumping of extended-release tablets. Constipation, nausea, sedation and itch are common. It should not be used with MAOIs. Never use non-medically alone. Have naloxone available.[5][6][3]

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.
Interactions & Contraindications

Drug interactions

Benzodiazepines, Alcohol, Gabapentinoids (gabapentin, pregabalin) Life-threatening additive respiratory depression and sedation (FDA boxed warning), the leading cause of opioid death.[3]
Alcohol Alcohol can cause 'dose dumping' of extended-release oxymorphone: even a single drink can release much of the ER dose at once, sharply raising peak levels.[3][6]
Opioids Additive effects with other opioids.[3]
MAOIs, Other serotonergic drugs Risk of severe reactions. Avoid within 14 days of an MAOI.[3]

Contraindications

Significant respiratory depression or acute severe asthma or acute/severe bronchial asthma in an unmonitored setting.[3]
Paralytic ileus or gastrointestinal obstruction paralytic ileus or known/suspected GI obstruction.[3]
Kidney or liver impairment moderate-to-severe hepatic impairment (markedly increased exposure).[3]
Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent or recent (within 14 days) MAOI use.[3]
Head injury or raised intracranial pressure head injury or raised intracranial pressure.[3]
Combining with alcohol or other CNS depressants any concurrent CNS depressant or alcohol, and caution in the elderly and renal impairment.[3]
Usage & Context
  • A high-potency strong opioid analgesic for moderate-to-severe pain: used as immediate-release tablets and by injection (IM/IV/subcutaneous), and formerly as 12-hourly extended-release tablets (Opana ER).
  • Heavily misused by the oral, intranasal and, after the 2012 reformulation, injection routes. Injection misuse of Opana ER drove HIV and hepatitis-C outbreaks, leading the FDA to request its withdrawal in 2017.
  • Sold under the brand names Opana and Numorphan.
Sources & Evidence

Further Information