Agopose tablets

Agomelatine......25mg

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

5. Pathophysiology

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

7. Mechanism of Action 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. Agomelatin strongly binds to and stimulates the activity of MT1 and MT2 receptors normalizing the disturbed Circadian Rhythmus and Disrupted Sleep Wake Cycles. Agomelatin does not inhibit the uptake of Serotonin, Norepinephrine or Dopamine. 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 Antagonism increases norepinephrine and dopamine level the frontal cortex of the brain. These action of agomelatin produce antidepressant, Antianxiety and also increase Slow Wave Sleep which is decrease in depression. It can increase neurogenesis in the hippocampus and may also have neuroprotective effect which might also contributes to its antidepressant effect.

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

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

13. Excretion 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. Also excreted in feces.

14. Drug interaction 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. Fluxomine and oestrogens have been found to increase the level of agomelatine because of the enzyme inhibition.

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

16. Advantages The patient of depression dose not need dose tapering on agomelatine therapy. Serotonin syndrome, suicidal tenderness cardiovascular effects and weight gain have not been observed. Efficiency is similar to SSRIs and relapse rate is less compare to all other antidepressant. 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 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. However the limitation with agomelatin is lack of long term active comparator controls studies.

19. References Rouillon F., CNS Drug 2009, 23 suppl.2, 1-2. Poongothai,s ., pradeepa , R., ganesan,A.,Mohan , V., Plos one 2009, 4,e7185. Popoli , M., CNS Drug 2009 ,23 suppl.2,27-34. Howland,R.H ., Neuropsychiatric disease and Treatment 2009,5,563-576. Landolt,H.P ., Wehrle,R ., Eur J Neurosci 2009, 29, 1795-1709.