Agomalatine

Agomalatine Uses, Dosage, Side Effects, Food Interaction and all others data.

This compound binds to the melatoninergic receptors and the serotoninergic 5-HT2c receptor giving rise to the Melatonin Agonist and Selective Serotonin Antagonist (MASSA) concept. The melatoninergic receptors MT1 and MT2, are G protein coupled receptors and they act through decreasing cAMP and cGMP. Agomalatine strongly binds to and stimulates the activity of MT1 and MT2 receptors normalizing the disturbed circadian rhythms and disrupted sleep-wake cycles. Unlike the existing antidepressants, agomelatine does not inhibit the uptake of serotonin, norepinephrine or dopamine. It inhibits 5HT-2C receptor (G protein coupled receptor which increases IP3/DAG secondary messenger system) found abundantly in the SCN, frontal cortex, hippocampus and basal ganglia involved in the mood, motor and cognitive deficits associated with depressive states. 5HT-2C receptor antagonism increases norepinephrine and dopamine levels in the frontal cortex of the brain. This action of agomelatine produces antidepressant, antianxiety and also increases slow-wave sleep which is decreased in depression. It has been observed that it can increase neurogenesis in the hippocampus and may also have neuroprotective effects (by influencing glutamate release, glucocorticoid receptor gene expression and various neurotropic factors) which might also contribute to its antidepressant effects. A study has shown that agomelatine alleviates sleep disturbances after one week of therapy and by two weeks antidepressant effects manifest. The combined actions of agomelatine at MT1, MT2, and 5HT-2C receptors can improve the disturbed circadian rhythm and abnormal sleep pattern thus produce the antidepressant effect. These unique effects suggest that it might be effective for the treatment of seasonal affective disorder like anxiety and bipolar depression.

Agomalatine resynchronises circadian rhythms in animal models of delayed sleep phase syndrome and other circadian rhythm disruptions. It increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin. Agomalatine has shown an antidepressant-like effect in animal depression models, (learned helplessness test, despair test, and chronic mild stress) circadian rhythm desynchronisation, and in stress and anxiety models. In humans, agomelatine has positive phase shifting properties; it induces a phase advance of sleep, body temperature decline and melatonin onset. Controlled studies in humans have shown that agomelatine is as effective as the SSRI antidepressants paroxetine and sertraline in the treatment of major depression

Agomalatine
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Agomalatine
Generic	Agomelatine
Agomelatine Other Names	Agomelatina, Agomelatine
Type
Formula	C₁₅H₁₇NO₂
Weight	Average: 243.301 Monoisotopic: 243.125928793
Protein binding	> 95%
Groups	Approved, Investigational
Therapeutic Class	Atypical anti-depressant drugs
Manufacturer
Available Country	Russia
Last Updated:	September 19, 2023 at 7:00 am

Uses

Agomalatine is used for:

Major depressive disorder especially in non-responders and intolerant to SSRIs
Generalized anxiety disorder
Bipolar depression
Sleep disturbances
Seasonal affective disorder
Migraine and cluster headaches

Agomalatine is also used to associated treatment for these conditions: Major Depressive Episode

How Agomalatine works

The novel antidepressant agent, agomelatine, behaves as an agonist at melatonin receptors (MT1 and MT2) and as an antagonist at serotonin (5-HT)(2C) receptors.

Dosage

Agomalatine dosage

The effective dose of agomelatine is 25 mg per day given once at bed time for two weeks and can be increased to 50 mg per day in patients with inadequate response. Night time dosing is recommended because agomelatine improves the quality of sleep without day time sedation.

For oral administration with or without food. Most adult patients should take a dosage of 25 mg (one tablet) daily. It is usually taking prior to bed time. If no improvement is noticed after two weeks, the dosage can be increased to 50 mg (two tablets) daily.

Side Effects

The commonly reported adverse effects in the clinical trials of agomelatine are headache, nausea and diarrhea.

Precaution

It is found to increase the level of liver enzymes and so monitoring of enzyme level is warranted before starting therapy and therefore every 6 weeks.

Interaction

Potential interactions affecting agomelatine: Agomalatine is metabolised mainly by cytochrome P450 1A2 (CYP1A2) (90%) and by CYP2C9 (10%). Medicinal products that interact with these isoenzymes may decrease or increase the bioavailability of agomelatine. Fluvoxamine, a potent CYP1A2 and moderate CYP2C9 inhibitor markedly inhibits the metabolism of agomelatine resulting in a 60-fold (range 12-412) increase of agomelatine exposure. Consequently, co-administration of agomelatine with potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin) is contraindicated.

Elimination Route

Bioavailability is less than 5%.

Half Life

<2 hours

Pregnancy & Breastfeeding use

Use in pregnancy: For agomelatine, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see Toxicology: Preclinical Safety Data under Actions). Caution should be exercised when prescribing to pregnant women.

Use in lactation: It is not known whether Agomalatine is excreted into human milk. agomelatine or its metabolites are excreted in the milk of lactating rats. Potential effects of agomelatine on the breastfeeding infant have not been established. If treatment with agomelatine is considered necessary, breastfeeding should be discontinued.

Contraindication

It is contraindicated in patients with hepatic impairment and hypersensitivity to the active substances or any of the excipients.

Special Warning

Children under 18 years: Should be given only on medical advice.

Children and adolescents: Agomalatine is not recommended in the treatment of depression in patients

Use in the elderly: Efficacy has not been clearly demonstrated in the elderly (65 years). Only limited clinical data is available on the use of Agomalatine in elderly patients 65 years with major depressive episodes. Therefore, caution should be exercised when prescribing Agomalatine to these patients.

Acute Overdose

There is limited experience with agomelatine overdose. During the clinical development, there were a few reports of agomelatine overdose, taken alone (up to 450 mg) or in combination (up to 525 mg) with other psychotropic medicinal products. Signs and symptoms of overdose were limited and included drowsiness and epigastralgia. No specific antidotes for agomelatine are known. Management of overdose should consist of treatment of clinical symptoms and routine monitoring. Medical follow-up in a specialised environment is recommended.