Morphine !

The reference opioid for severe pain and cancer pain. It activates the μ receptor; it can depress breathing and causes constipation.

Updated 2026-11-01

Class: Opioids and antagonists
Receptor: μ-opioid receptor
ATC code: N02AA01
WHO Model List of Essential Medicines

μ-opioid receptorMorphine

The figure shows morphine in the μ receptor bound to its Gi protein; the viewer crops the image to the receptor.

Target in 3D: μ-opioid receptor. PDB structure 8EF6 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Morphine, a natural opium alkaloid, is a full agonist at the μ receptor. It activates the Gi protein, which closes presynaptic calcium channels and opens potassium channels, reducing pain transmission in the spinal cord and brainstem; it also changes the emotional experience of pain. The same receptors in the brainstem and gut explain respiratory depression, miosis and constipation.

Binds and activates the μ receptor on pain-pathway neurons
The Gi protein closes Ca²⁺ channels and opens K⁺ channels
Less glutamate and substance P are released in the dorsal horn
Relief of severe pain; in the brainstem, less drive to breathe

Pharmacokinetics

Absorption: Less drug reaches the blood by mouth because of hepatic first-pass metabolism.
Metabolism: Liver, mainly by glucuronidation (UGT2B7): morphine-3-glucuronide, inactive, and morphine-6-glucuronide, active.
Elimination: Kidney, mainly as glucuronides, which build up in kidney disease.
Half-life: Between 1.5 and 4.5 hours, depending on the study.
Onset and duration: Intravenously, the peak effect on the nervous system takes about 30 minutes.

Indications

Pain of acute myocardial infarction Myocardial Infarction (Heart Attack) →
Cancer pain, such as that of advanced lung cancer Lung cancer →
Severe acute postoperative or trauma pain
Breathlessness in palliative care

Adverse effects

Common

Constipation
Nausea and vomiting
Drowsiness
Itching from histamine release
Urinary retention
Miosis

Contraindications

Significant respiratory depression without monitoring or support
Severe acute asthma
Paralytic ileus or bowel obstruction
Use of monoamine oxidase inhibitors within the last two weeks

Key interactions

Benzodiazepines, alcohol and other CNS depressants: Add sedation and respiratory depression, with risk of death.
Monoamine oxidase inhibitors: Severe reactions, with high or low blood pressure and CNS depression.
Naloxone: Reverses its effects and can precipitate withdrawal in dependent patients.

What is monitored

Respiratory rate and sedation level
Bowel habit
Kidney function

Test yourself

Think of the answer, then tap the question to see it.

Why can morphine cause excessive, prolonged sedation in a patient with chronic kidney disease?

Its active metabolite, morphine-6-glucuronide, is cleared by the kidney and builds up when kidney function falls, intensifying and prolonging the opioid effect.

What explains the itching, flushing and orthostatic hypotension morphine sometimes causes?

Histamine release and peripheral vasodilation.

Why does oral morphine need more drug than intravenous morphine for the same effect?

Because much of the morphine absorbed from the gut is metabolized in the liver before it reaches the circulation (first-pass effect).

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Morphine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); MORPHINE SULFATE injection (DailyMed (U.S. National Library of Medicine), 2026); Morphine (PubChem (NCBI), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.