Noradrenaline (also known as norepinephrine) is a vital neurotransmitter and hormone that plays a central role in regulating your alertness, stress response, attention, energy metabolism, and cardiovascular function. It is part of the body’s "fight-or-flight" system and is closely related to both dopamine and adrenaline.
How noradrenaline is produced, broken down, transported, and received in the body depends on a series of enzymes, transporters, receptors, nutrients, and genetic factors. Here’s a breakdown of how this system works and why it matters for mental and physical health.
🧬 Step 1: From Dopamine to Noradrenaline – The DBH Enzyme
Noradrenaline is synthesized from dopamine via the enzyme Dopamine Beta-Hydroxylase (DBH).
- Dopamine → Noradrenaline
- Enzyme: DBH
- Cofactors: Copper and Vitamin C
Genetic variants in the DBH gene or nutrient deficiencies can lead to reduced conversion, potentially contributing to dopamine excess or noradrenaline deficiency.
🧠 Step 2: From Noradrenaline to Adrenaline – The PNMT Enzyme
Noradrenaline can be methylated into adrenaline (epinephrine) through the action of the enzyme Phenylethanolamine N-Methyltransferase (PNMT).
- Noradrenaline → Adrenaline
- Enzyme: PNMT
- Cofactor: SAMe (S-adenosylmethionine)
Key points:
- PNMT is methylation-dependent
- Genetic variants can slow this enzyme, increasing the demand for SAMe
- Chronic stress depletes SAMe, which may impair adrenaline production and stress resilience
🚚 Noradrenaline Reuptake – The NET Transporter (SLC6A2)
The norepinephrine transporter (NET) is responsible for reuptake—removing noradrenaline from the synapse after it has done its job.
- Gene: SLC6A2
- Function: Clears noradrenaline from the synapse
Genetic variants:
- SNPs in SLC6A2 can lead to increased NET activity, which reduces noradrenaline availability
- This is associated with:
- Depression
- Fatigue
- ADHD
- Orthostatic intolerance
- Depression
💊 Medications and Natural Inhibitors of NET
To increase noradrenaline levels, some therapies focus on inhibiting its reuptake:
🧪 Vesicular Storage – The Role of VMAT1 (SLC18A1)
Before noradrenaline (and serotonin) can be released, they must be packaged into vesicles by VMAT1, a vesicular monoamine transporter.
- Gene: SLC18A1
- Function: Transfers monoamines into vesicles for release
- SNPs that upregulate VMAT1 are usually considered beneficial, as they promote healthy neurotransmitter release
🎯 Noradrenaline and Adrenaline Receptors – ADRB1 and ADRB2
Noradrenaline and adrenaline act on adrenergic receptors (ADRB), which determine the effect of the signal on the body and brain.
🧬 Types of ADRB Receptors:
Genetic variants:
- SNPs that upregulate ADRB1 or ADRB2 increase sensitivity to noradrenaline/adrenaline
- This may heighten the effects of stress, stimulation, or pharmacological drugs
Medication relevance:
- Beta blockers (like propranolol) antagonize ADRB1 → reduce heart rate and anxiety
- ADRB2 is a common target of anesthetics for sedation and pain relief
🧾 Summary Table
🧠 Final Thoughts
Noradrenaline is a multifunctional molecule that impacts everything from brain function and blood pressure to focus, emotional resilience, and stress recovery. Its effectiveness is shaped by:
- Enzymes like DBH and PNMT
- Transporters like NET and VMAT1
- Receptors ADRB1 and ADRB2
- Genetic SNPs, nutrient availability, and stress levels
Whether you're dealing with fatigue, anxiety, ADHD, or low resilience to stress, understanding your noradrenaline system can offer a powerful lens for targeted, functional interventions.