How Does Circadin (Melatonin) Work? Mechanism of Action & Metabolic Effects
A detailed look at the chemical composition, mechanism of action, and metabolic effects of melatonin in Circadin prolonged-release tablets.
Key Takeaways
- Natural Hormone: Melatonin is a naturally occurring hormone that regulates sleep-wake cycles.
- Mechanism: Works by binding to melatonin receptors in the brain's suprachiasmatic nucleus, promoting sleepiness.
- Prolonged-Release: Special formulation provides controlled release throughout the night for sustained effect.
- Metabolism: Primarily metabolised in the liver via cytochrome P450 enzymes.
- Key Consideration: Specifically indicated for primary insomnia in patients aged 55 years and older.
Circadin contains melatonin, a hormone naturally produced by the pineal gland in the brain. It is used for the short-term treatment of primary insomnia in patients aged 55 years and older, working with your body's natural sleep-wake cycle to promote restful sleep.
Chemical Composition of Circadin
Circadin is a prolonged-release tablet containing melatonin as its active ingredient. The formulation is designed to release melatonin gradually throughout the night to mimic the body's natural melatonin secretion pattern.
| Component | Amount/Type | Function |
|---|---|---|
| Melatonin (active substance) | 2 mg | Regulates sleep-wake cycle |
| Ammonio methacrylate copolymer type B | Not specified | Prolonged-release matrix former |
| Calcium hydrogen phosphate dihydrate | Not specified | Filler/binder |
| Lactose monohydrate | Not specified | Filler |
| Silica (colloidal anhydrous) | Not specified | Glidant |
| Talc | Not specified | Lubricant |
| Magnesium stearate | Not specified | Lubricant |
Prolonged-Release Mechanism
The special formulation of Circadin allows melatonin to be released gradually over several hours. The ammonio methacrylate copolymer creates a matrix that controls the diffusion of melatonin, ensuring sustained plasma concentrations throughout the night.
Mechanism of Action: Regulating Sleep-Wake Cycles
Circadin works by supplementing the body's natural melatonin production, which typically decreases with age. It helps to synchronize the circadian rhythm, particularly in older adults who may have impaired melatonin secretion.
Receptor Binding
Action: Melatonin binds to specific melatonin receptors (MT1 and MT2) in the suprachiasmatic nucleus of the brain.
Effect: MT1 receptor activation promotes sleepiness by inhibiting neuronal firing, while MT2 receptor involvement helps synchronize the circadian clock.
Result: This binding initiates a cascade of events that signal the body it's time to sleep, reducing sleep latency (time to fall asleep).
Circadian Rhythm Regulation
Action: Melatonin adjusts the timing of the internal biological clock.
Effect: It helps align circadian rhythms with the external light-dark cycle, particularly important for those with disrupted sleep patterns.
Result: Improved sleep quality and duration, with more appropriate timing of sleep phases.
Body Temperature Modulation
Action: Melatonin causes a slight decrease in core body temperature.
Effect: This temperature drop is a physiological signal that facilitates sleep initiation and maintenance.
Result: The body enters a state more conducive to sleep, similar to the natural temperature dip that occurs at night.
Visualizing the Mechanism
Fig 1. Molecular structure of melatonin (N-acetyl-5-methoxytryptamine)
Melatonin (C13H16N2O2)
O
||
CH3-O-◻-CH2-CH2-N-C-CH3
| ||
H O
Indole structure with methoxy and acetyl groups
Metabolic Pathway & Systemic Effects
After oral administration, melatonin is extensively metabolized, primarily in the liver, with only about 15% reaching systemic circulation unchanged.
Melatonin Metabolism
- Primary Pathway: Melatonin is primarily metabolized in the liver by cytochrome P450 enzymes, mainly CYP1A2.
- Initial Metabolism: It is hydroxylated at the 6-position to form 6-hydroxymelatonin.
- Conjugation: 6-hydroxymelatonin is then conjugated with sulfate to form 6-sulfatoxymelatonin, the main urinary metabolite.
- Alternative Pathway: A small portion is demethylated to N-acetylserotonin.
- Excretion: Metabolites are primarily excreted in the urine (90%), with a small amount in faeces.
Pharmacokinetics
Due to its prolonged-release formulation, Circadin has different pharmacokinetic properties compared to immediate-release melatonin:
- Absorption: Following oral administration, melatonin is absorbed with an absolute bioavailability of approximately 15%.
- Tmax: Maximum plasma concentrations are reached about 2-3 hours after administration.
- Half-life: The elimination half-life is approximately 3.5-4 hours, but the prolonged-release formulation maintains effective concentrations throughout the night.
- Food Effect: Administration after food may delay absorption but does not significantly affect overall bioavailability.
Several substances can affect melatonin metabolism. Fluvoxamine (an SSRI) can increase melatonin concentrations by inhibiting CYP1A2 and CYP2C19. Smoking may decrease melatonin effectiveness by inducing CYP1A2. Alcohol should be avoided as it reduces the effectiveness of Circadin.
Safety Profile & Contraindications
Appropriate Use Cases
Primary insomnia in patients aged 55 years and older
Short-term treatment (up to 13 weeks)
Sleep initiation and maintenance difficulties
Absolute Contraindications
Hypersensitivity to melatonin or any excipients
Autoimmune diseases (due to lack of safety data)
Children and adolescents (0-18 years)
Special Precautions
Liver or kidney impairment (use not recommended)
Pregnancy and breastfeeding (should be avoided)
Driving or operating machinery (may cause drowsiness)
Reported Side Effects
| Frequency | Side Effects | Management |
|---|---|---|
| Common (≥1/100 to <1/10) | Headache, pharyngitis, back pain, asthenia | Usually mild and transient |
| Uncommon (≥1/1,000 to <1/100) | Irritability, nervousness, restlessness, insomnia, abnormal dreams, dizziness, migraine, hypertension, abdominal pain, mouth ulceration, dry mouth, skin inflammation, night sweats, pruritus, rash, pain in extremities, weight increased | Consult doctor if persistent |
| Rare (≥1/10,000 to <1/1,000) | Chest pain, angina pectoris, palpitations, depression, visual impairment, blurred vision, disorientation, vertigo, haematuria, leucopenia, thrombocytopenia, psoriasis | Seek medical attention |
Frequently Asked Questions
How is Circadin different from regular melatonin supplements?
Circadin is a prescription medicine with a specific prolonged-release formulation that delivers melatonin gradually over several hours to mimic the body's natural release pattern. This differs from over-the-counter melatonin supplements which are typically immediate-release and may not provide the same sustained effect throughout the night. Circadin is also specifically approved for treating primary insomnia in patients aged 55 and over.
Why is Circadin only recommended for people aged 55 and older?
Natural melatonin production typically decreases with age. Clinical trials demonstrating Circadin's efficacy primarily focused on this older population who often experience age-related decline in melatonin secretion. While melatonin may benefit younger individuals with certain sleep disorders, Circadin is specifically licensed for use in those 55 and older based on the available evidence from clinical studies.
Can I drink alcohol while taking Circadin?
No, you should avoid alcohol before, during, or after taking Circadin. Alcohol can reduce the effectiveness of Circadin and may increase the risk of side effects such as dizziness and drowsiness. Combining alcohol with any sleep medication is generally not recommended as it can impair your coordination, judgment, and exacerbate sleep problems.
How long does it take for Circadin to start working?
Circadin is designed to be taken 1-2 hours before bedtime. The prolonged-release formulation begins working within this timeframe, with peak concentrations reached about 2-3 hours after administration. However, individual responses may vary. It's important to take Circadin consistently as prescribed rather than expecting immediate results after a single dose.
What should I do if I miss a dose of Circadin?
If you forget to take your Circadin tablet, take it as soon as you remember, but only if it's still before your bedtime. If it's already the next day or nearly time for your next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for a forgotten one. If you're unsure, consult your pharmacist or doctor for advice.
Need Treatment for Jet Lag
If you're experiencing sleep difficulties, our UK-registered doctors can help determine if Circadin (Melatonin) Tablets is appropriate for your condition through a confidential online consultation.
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Medical Content Manager
Nabeel is a co-founder and medical content manager of Chemist Doctor. He works closely with our medical team to ensure the information is accurate and up-to-date.
Medical Doctor
Dr. Feroz is a GMC-registered doctor and a medical reviewer at Chemist Doctor. He oversees acute condition and urgent care guidance.
Medical Director
Usman is a co-founder and medical director of Chemist Doctor. He leads the organisation's strategic vision, bridging clinical and operational priorities.
Review Date: 29 October 2025
Next Review: 30 April 2026
Published on: 29 October 2025
Last Updated: 30 October 2025
