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| Name | Mirtazapine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB00370 (APRD00685) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Groups | approved | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | Mirtazapine is an antidepressant introduced by Organon International in 1996 used for the treatment of moderate to severe depression. Mirtazapine has a tetracyclic chemical structure and is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). It is the only tetracyclic antidepressant that has been approved by the Food and Drug Administration to treat depression. [Wikipedia] |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Synonyms |
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| Brand name mixtures | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| CAS number | 61337-67-5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 265.3529 Monoisotopic: 265.157897623 |
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| Chemical Formula | C17H19N3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=RONZAEMNMFQXRA-UHFFFAOYSA-N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI |
InChI=1S/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3
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| IUPAC Name |
5-methyl-2,5,19-triazatetracyclo[13.4.0.0^{2,7}.0^{8,13}]nonadeca-1(19),8(13),9,11,15,17-hexaene
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| SMILES |
CN1CCN2C(C1)C1=C(CC3=CC=CN=C23)C=CC=C1
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| Mass Spec | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Taxonomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Pharmacology | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Indication | For the treatment of major depressive disorder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Mirtazapine, an antidepressant of the piperazinoazepine class, is a tetracyclic compound with an anxiolytic effect. Mirtazapine has fewer ADRs than tricyclic antidepressants and is better tolerated. Selective blockade of specific serotonin receptors by mirtazapine likey minimizes side effects typical of other antidepressants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mechanism of action | 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Absorption | Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Volume of distribution | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Protein binding | 85% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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.
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| Route of elimination | This drug is known to be substantially excreted by the kidney (75%). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Half life | 20-40 hours | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clearance | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Toxicity | Symptoms of overdose include disorientation, drowsiness, impaired memory, and tachycardia. LD50 is 600-720mg/kg (oral, mice) and 320-490mg/kg (oral, rat) [PMID: 10333982] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Pathways | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| State | solid | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Melting point | 114-116oC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Synthesis Reference | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| General Reference |
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| PDB Entries | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| FDA label | show (904.1 KB) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MSDS | show (57.2 KB) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Drug Interactions | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Targets |
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1. 5-hydroxytryptamine 2A receptor Pharmacological action: yesActions: antagonist This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production Organism class: humanUniProt ID: P28223 ![]() Gene: HTR2A ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. 5-hydroxytryptamine 3 receptor Pharmacological action: yesActions: antagonist This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel Organism class: humanUniProt ID: P46098 ![]() Gene: HTR3A ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
3. Alpha-2A adrenergic receptor Pharmacological action: yesActions: antagonist Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol Organism class: humanUniProt ID: P08913 ![]() Gene: ADRA2A ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
4. 5-hydroxytryptamine 2C receptor Pharmacological action: unknownActions: antagonist This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system Organism class: humanUniProt ID: P28335 ![]() Gene: HTR2C ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Pharmacological action: unknown
Actions: agonist Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions Organism class: humanUniProt ID: P41145 ![]() Gene: OPRK1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Pharmacological action: no
Actions: antagonist In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system Organism class: humanUniProt ID: P35367 ![]() Gene: HRH1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Enzymes |
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Actions: substrate, inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684![]() Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate, inhibitor, inducer
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants UniProt ID: P10635![]() Gene: CYP2D6 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen UniProt ID: P05177![]() Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan UniProt ID: P11712![]() Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol) UniProt ID: P10632![]() Gene: CYP2C8 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.