Pharmacology · Topic
Adrenergic transmission !
How the body makes, releases, recycles and breaks down noradrenaline and adrenaline, and how drugs act on each step.
Updated 2026-11-01
Noradrenaline is the transmitter of most sympathetic postganglionic neurons, and the adrenal medulla adds adrenaline to the blood. Both are catecholamines built from tyrosine. Their action ends mainly by reuptake into the nerve terminal, not by breakdown in the cleft. Drugs can act on synthesis, storage, release, reuptake, breakdown or the receptors themselves.
Step by step
- Tyrosine enters the neuron and is hydroxylated to DOPA
- DOPA is decarboxylated to dopamine in the cytoplasm (aromatic L-amino acid decarboxylase)
- Dopamine enters vesicles through VMAT and becomes noradrenaline (dopamine beta-hydroxylase)
- In the adrenal medulla, PNMT converts noradrenaline to adrenaline
- Calcium entry triggers release; presynaptic alpha-2 receptors give negative feedback
- NET reuptake ends most of the signal; MAO and COMT break down the rest
Drugs at each step
- Synthesis: methyldopa forms a false transmitter that acts as a central alpha-2 agonist
- Storage: reserpine depletes vesicles (historical antihypertensive)
- Release: amphetamine, ephedrine and tyramine displace noradrenaline
- Reuptake: cocaine, tricyclic antidepressants and SNRIs block NET
- Breakdown: MAO inhibitors raise catecholamines; selegiline is selective for MAO-B at usual doses
- Receptors: direct agonists (noradrenaline, adrenaline, phenylephrine, salbutamol) and antagonists (alpha and beta blockers)
Classic clinical links
With a non-selective MAO inhibitor, tyramine from aged cheese, cured meats or fermented foods escapes breakdown in the gut and liver, releases large amounts of noradrenaline and can cause a hypertensive crisis. Cocaine blocks reuptake of noradrenaline and dopamine, giving tachycardia, hypertension and vasoconstriction. Indirect agents lose effect with repeated doses as stores run down (tachyphylaxis).
Dopamine as a drug
Dopamine is both a precursor of noradrenaline and a transmitter in its own right. Given intravenously it does not cross the blood–brain barrier; its effects depend on the level, acting on dopamine receptors, then on beta-1, then on alpha-1 receptors as the infusion rises.
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme is the rate-limiting step in catecholamine synthesis?
Tyrosine hydroxylase, which converts tyrosine to DOPA.
What mainly ends the action of noradrenaline released at a synapse?
Reuptake into the nerve terminal by the noradrenaline transporter (NET), rather than enzymatic breakdown in the cleft.
Why can aged cheese cause a hypertensive crisis in a patient taking a non-selective MAO inhibitor?
Tyramine is not broken down by MAO in the gut and liver, reaches nerve terminals and releases large amounts of noradrenaline.
How does reserpine lower blood pressure?
It blocks VMAT, so noradrenaline cannot be stored in vesicles and nerve terminals are depleted.
Related classes
- Vasopressors and inotropes
- Beta blockers
- Alpha blockers
- Centrally acting antihypertensives
- Monoamine oxidase inhibitors (MAOIs)
Example drugs
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DBH gene: MedlinePlus Genetics (MedlinePlus Genetics (U.S. National Library of Medicine), 2026); 15.4 Drugs that Affect the Autonomic System (OpenStax (Rice University), 2022); 15.1 Divisions of the Autonomic Nervous System (OpenStax (Rice University), 2022).
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Representative model, for educational purposes only.