Agomelatine tablets are used to treat depression and improve sleep. It works by improving the release of dopamine, norepinephrine, and melatonin. It binds to melatonin receptors MT1 and MT2 and the 5-HT2C serotonin receptor. This helps normalize circadian rhythms and sleep-wake cycles. It is effective for treating major depressive disorder, especially in those who do not respond to SSRIs, as well as generalized anxiety disorder, bipolar depression, sleep disturbances, and migraines. Common side effects include headache, nausea, dizziness, and dry mouth.

1. AGOPOSE TABLETS
Controls Depression, Improve Sleep
Prepared By: Astha Sanyal
M.Pharm sem:2(QA)
Shri Sarvajanik Pharmacy College, Mehsana

2. COMPOSITION
Each film coated tablet contains:
Agomelatine…….25mg

3. Dose: 25 mg OD at Bed time
Dose can be increase to 50mg after 4 weeks
Duration: 8 Weeks to 24Weeks
Max. Duration: 24 Weeks.
Category:- Norepinephrine Dopaminergic
Disinhibitory Antidepressant (NDDI)
Indication: Depression with Comorbid
Insomnia
Contraindication:- Hypersensitivity

4. Uses
O Major depressive disorder especially in
non responder and intolerant to SSRIs.
O Generalized anxiety disorder.
O Bipolar depression.
O Sleep disturbance.
O Migraine and cluster headache.

5. Pathophysiology

6. Mode of Action
O Improves release of Dopamine and
Norepinephrine; Thus, control Depression
O Improve release of Melatonin; thus control
Insomnia

7. Mechanism of Action
O Compounds binds to Melatoninergic
Receptor and the Serotoninergic 5HT-2C
receptor giving rise to the melatonin
agonist and selective serotonin antagonist
(MASSA) concept.

8. MELATONINERGIC
RECEPTORS
They are the MT1 and MT2 are GPCR and they acts
through decreasing Cyclic AMP and Cyclic GMP.
O Agomelatin strongly binds to and stimulates the
activity of MT1 and MT2 receptors normalizing the
disturbed Circadian Rhythmus and Disrupted
Sleep Wake Cycles.
O Agomelatin does not inhibit the uptake of
Serotonin, Norepinephrine or Dopamine.
O It inhibits 5HT-2C receptors found abundantly in
SCN, frontal cortex, hippocampus and Basal
ganglia involved in the mood, motor and cognitive
deficit associated with depressive states.

9. Serotoninergic 5HT-2C
Receptors
O Antagonism increases norepinephrine and
dopamine level the frontal cortex of the brain.
O These action of agomelatin produce
antidepressant, Antianxiety and also increase
Slow Wave Sleep which is decrease in
depression.
O It can increase neurogenesis in the
hippocampus and may also have
neuroprotective effect which might also
contributes to its antidepressant effect.

10. Combined Action
O Agomelatin at MT2, MT1 and 5HT-2C
receptor can improve the disturb circadian
rhythm and abnormal sleep pattern thus
produced the Antidepressants effect.
O These unique effects suggest that it might
be effective for the treatment of seasonal
affective disorder like anxiety and bipolar
depression.

11. Pharmacokinetics
O Agomelatin on oral administration is rapidly
absorb with bioavaiblity of more than 78%.
ABSORPTION
Food slows the absorption of agomelatin,but it is
clinically in significant.
It peaks in plasma after 1to2 hr following oral
administration.
More than 95% plasma protine bonds with 35%
bonds to albumin and 36% bond to α-1acid
glycoprotin.

12. Distribution and Metabolism
O Volume of distribution around 35L.
O 90% of administer dose is metabolite by
cytochrome P450 1A2 isoenzymes to 7-O-
dmethylated and hydroxylated in active
metabolites.
O It is also metabolized to 3,4 dyhydrodiols.

13. Excretion
O About 61 to 81% of the dose is excreted
as metabolites in urine over the first 24hr
with the mean terminal half life of 2to3hr.
O Also excreted in feces.

14. Drug interaction
O Dose not induced and inhibit the
cytochrome P450 enzyme but enzyme
inducers like omeprazole and nicotine
decrease the serum level of agomelatin
hence the dose has to be increase to
50mg per day when this drugs are
concomitantly taken.
O Fluxomine and oestrogens have been
found to increase the level of agomelatine
because of the enzyme inhibition.

15. Adverse effect
O Headache
O Nausea
O Dizziness
O Dry mouth
O Diarrhea
O Insomnia
O Somnolence
O Constipation
O Fatigue
O Upper abdominal pain

16. Advantages
O The patient of depression dose not need
dose tapering on agomelatine therapy.
O Serotonin syndrome, suicidal tenderness
cardiovascular effects and weight gain
have not been observed.
O Efficiency is similar to SSRIs and relapse
rate is less compare to all other
antidepressant.
O Improves quality of a sleep without day
time sedation.

17. Risk Categories
Pregnancy Category B
Pediatrics Not safe(can be used above
18 year of age)
Lactation With caution
Elderly Not recommended above 65
years old
Cardiac Safe
diabetic With caution

18. Conclusion
O Agomelain is a novel atypical
antidepressant with the unique
pharmacological that regulates the
circadian rhythmus with a relatively benign
tolerability profile making it an effective
alternative for patient who do not respond
to or can not tolerate currently available
antidepressant agent.
O However the limitation with agomelatin is
lack of long term active comparator
controls studies.

19. References
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O Poongothai,s., pradeepa, R.,
ganesan,A.,Mohan, V., Plos one 2009,
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O Popoli, M., CNS Drug 2009 ,23 suppl.2,27-
34.
O Howland,R.H., Neuropsychiatric disease and
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O Landolt,H.P., Wehrle,R., Eur J Neurosci 2009,
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