Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Mirtazapine is extensively metabolized by demethylation and hydroxylation followed by glucuronide conjugation. Cytochrome P450 2D6 and cytochrome P450 1A2 are involved in formation of the 8-hydroxy metabolite of mirtazapine, and cytochrome P450 3A4 is responsible for the formation of the N-desmethyl and N-oxide metabolites. Several metabolites possess pharmacological activity, but plasma levels are very low. Route of Elimination: This drug is known to be substantially excreted by the kidney (75%). Half Life: 20-40 hours
- Uses/Sources: For the treatment of major depressive disorder.
- Symptoms: Symptoms of overdose include disorientation, drowsiness, impaired memory, and tachycardia.
- Treatment: Treatment should consist of those general measures employed in the management of overdose with any drug effective in the treatment of major depressive disorder. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion or exchange transfusion in the treatment of mirtazapine overdosage. No specific antidotes for mirtazapine are known. (L1712)
- Route of Exposure: Oral. Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%.
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 600-720mg/kg (oral, mice) (L1855) LD50: 320-490mg/kg (oral, rat) (L1855)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
5-hydroxytryptamine receptor 2B Sodium-dependent serotonin transporter Alpha-1A adrenergic receptor Sodium-dependent dopamine transporter Sodium-dependent noradrenaline transporter 5-hydroxytryptamine receptor 7 D(2) dopamine receptor D(3) dopamine receptor D(4) dopamine receptor Alpha-2B adrenergic receptor Beta-1 adrenergic receptor Beta-2 adrenergic receptor Alpha-2C adrenergic receptor D(1) dopamine receptor Alpha-1 adrenergic receptor Histamine H3 receptor |
15771415 9537821 10762339 12109911 20945968 10636247 8636062 3419539 8930006 |
|
5-hydroxytryptamine receptor 2A 5-hydroxytryptamine receptor 2C 5-hydroxytryptamine receptor 1A Alpha-2A adrenergic receptor Kappa-type opioid receptor Histamine H1 receptor 5-hydroxytryptamine receptor 3A |
Mirtazapine acts as an antagonist at central pre-synaptic alpha(2)-receptors, inhibiting negative feedback to the presynaptic nerve and causing an increase in NE release. Blockade of heteroreceptors, alpha(2)-receptors contained in serotenergic neurons, enhances the release of 5-HT, increasing the interactions between 5-HT and 5-HT1 receptors and contributing to the anxiolytic effects of mirtazapine. Mirtazapine also acts as a weak antagonist at 5-HT1 receptors and as a potent antagonist at 5-HT2 (particularly subtypes 2A and 2C) and 5-HT3 receptors. Blockade of these receptors may explain the lower incidence of adverse effects such as anxiety, insomnia, and nausea. Mirtazapine also exhibits significant antagonism at H1-receptors, resulting in sedation. Mirtazapine has no effects on the reuptake of either NE or 5-HT and has only minimal activity at dopaminergic and muscarinic receptors. |
10762339 17587360 11271412 11939713 10446735 12523492 14970364 10636247 24035337 9832994 8930006 10451911 10446738 15771415 12109911 11931344 10793320 11752352 14628003 12372565 14615872 11063897 16433010 10446734 |
Mirtazapine Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Cocaine dependence | 9.67 |
|
Diabetes Mellitus, Experimental | 9.57 |
|
Keratosis | 9.33 |
|
Phobic Disorders | 8.81 |
|
Dyskinesia, Drug-Induced | 8.67 |
|
Basal Ganglia Diseases | 8.41 |
|
Amphetamine-Related Disorders | 8.38 | |
Arthritis, Experimental | 8.29 |
|
Alcoholic liver cirrhosis | 8.24 |
|
Autism | 8.21 |
|
Pituitary Neoplasms | 7.98 |
|
Hyperkinesis | 7.43 |
|
Hepatocellular carcinoma | 6.97 |
|
Disruptive, Impulse Control, and Conduct Disorders | 6.93 |
|
Parkinson's disease | 6.83 |
|
Hyperprolactinemia | 6.69 |
|
Movement disorder | 6.64 |
|
LONG QT SYNDROME 13 | 6.6 |
|
Lymphoma, Large B-Cell, Diffuse | 6.49 |
|
Rheumatoid arthritis | 6.45 |
|