General
Preferred name
MIRTAZAPINE
Synonyms
mirtazepine(-) ()
Mirtazepine ()
6-Azamianserin ()
Org3770 ()
mirtazepine(+) ()
Org3770,6-Azamianserin ()
Avanza ()
Zispin ()
Rexer ()
Mirtazapin ()
Mirataz ()
ORG-3770 ()
Remeron Soltab ()
Remeron ()
Mirtazapine anhydrous ()
Promyrtil ()
ORG 3770 ()
Norset ()
Mirtazapine-d3 ()
Mirtazapine (CRM) ()
Mirtazapine-d3 (CRM) ()
P&D ID
PD000124
CAS
85650-52-8
207516-99-2
61337-67-5
1216678-68-0
Tags
natural product
drug
available
Approved by
FDA
First approval
1996
Drug Status
approved
vet_approved
Drug indication
Depression
Antidepressant
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA
**Summary**; ; The mechanism of action of mirtazapine is not fully understood[FDA label] but may be explained by its effects on central adrenergic and serotonergic activity. This drug exhibits a fast onset of action, a high level of response, a manageable side-effect profile, and dual noradrenergic and serotonergic effects that are unique from the effects of other antidepressants.[A177811]; ; **Effects on various receptors**; ; It has been shown that both noradrenergic and serotonergic activity increase following mirtazapine administration. The results of these studies demonstrate mirtazapine exerts antagonist activity at presynaptic α2-adrenergic inhibitory autoreceptors and heteroreceptors in the central nervous system. This is thought to lead to enhanced noradrenergic and serotonergic activity [FDA label], which are known to improve the symptoms of depression and form the basis of antidepressant therapy.[A178198, A178201]; ; Mirtazapine is a strong antagonist of serotonin 5-HT2 and 5-HT3 receptors. It has not been found to bind significantly to the serotonin 5-HT1A and 5-HT1B receptors [FDA label] but indirectly increases 5-HT1A transmission.[A4709] ; ; In addition to the above effects, mirtazapine is a peripheral α1-adrenergic antagonist. This action may explain episodes of orthostatic hypotension that have been reported after mirtazapine use.[FDA label] Mirtazapine is a potent histamine (H1) receptor antagonist, which may contribute to its powerful sedating effects.[FDA label] The pain-relieving effects of mirtazapine may be explained by its effects on opioid receptors.[A13073,A177868]
INDICATION
This drug is indicated for the treatment of major depressive disorder and its associated symptoms.[FDA label]; ; Mirtazapine has been used off-label for a variety of conditions including panic disorder, generalized anxiety disorder, dysthymia, tension headaches, hot flushes, post-traumatic stress disorder (PTSD), sleep disorders, substance abuse disorders, and sexual disorders, among others.[A177811,A177946]
ROE
This drug is mainly excreted by the kidney. It is 75% eliminated in the urine and 15% eliminated in the feces.[A177826]
METABOLISM
Mirtazapine is heavily metabolized in humans.[FDA label] Demethylation and hydroxylation and subsequent glucuronide conjugation are the major pathways by which mirtazapine is metabolized.[A177826,FDA label] Data from in vitro studies on human liver microsomes show that cytochrome 2D6 and 1A2 lead to the formation of the _8-hydroxy metabolite_ of mirtazapine. The CYP3A enzyme metabolizes this drug into its _N-desmethyl and N-oxide_ metabolites. There are various other unconjugated metabolites of this drug that are pharmacologically active, but are measured in the blood at limited concentrations.[FDA label, A177826]
ABSORPTION
The absorption of this drug is rapid and complete.[A177826, FDA label] Due to first pass metabolism in the liver and metabolism in the gut wall, absolute bioavailability is about 50%.[FDA label,A177826] Peak blood concentrations are attained within about 2 hours after an oral dose. Food has little effect on the absorption of mirtazapine, and no dose adjustment is required if it is taken with food.[FDA label] Steady-state levels are achieved by about 5 days after the initial dose.[FDA label, A177826] Mirtazapine pharmacokinetics vary across gender and age range. Females and the elderly population have been shown to have higher blood concentrations in comparison to males and younger adults.[A177826]
HALF-LIFE
20-40 hours [FDA label, A177826]
DESCRIPTION
Mirtazapine is a tetracyclic antidepressant with complex polypharmacology involving certain adrenergic and serotonin receptors . It also has strong antihistamine effects.
(GtoPdb)
PHARMACODYNAMICS
**General effects and a note on suicidality**; ; Mirtazapine is effective in treating moderate to severe depression and treats many symptoms normally associated with this condition. These symptoms may include disturbed sleep, lack of appetite, and anhedonia, in addition to anxiety.[A555,A178150,T595]. It is important to note that suicidal ideation and behavior may emerge or increase during treatment with mirtazapine, as with any other antidepressant. This risk is especially pronounced in younger individuals. Patients, medical professionals, and families should monitor for suicidal thoughts, worsening depression, anxiety, agitation, sleep changes, irritable behavior, aggression, impulsivity, restlessness, and other unusual behavior when this drug is taken or the dose is adjusted.[FDA label] Do not administer mirtazapine to children. When deciding to prescribe this drug, carefully consider the increased risk of suicidal thoughts and behavior, especially in young adults.[FDA label]; ; **Effects on appetite and weight gain**; ; In addition to the above effects, mirtazapine exerts stimulating effects on appetite, and has been used for increasing appetite and decreasing nausea in cancer patients.[A177952, A177958] Some studies and case reports have shown that this drug improves eating habits and weight gain in patients suffering from anorexia nervosa when administered in conjunction with psychotherapy and/or other psychotropic drugs.[A177961,A178186] In a clinical trial, women with depression experienced a clinically significant mean increase in body weight, fat mass, and concentrations of leptin when treated with mirtazapine for a 6-week period, with a lack of effect on glucose homeostasis.[A177970]; ; **Effects on sleep**; ; The use of mirtazapine to treat disordered sleep has been leveraged from its tendency to cause somnolence, which is a frequently experienced adverse effect by patients taking this drug.[A177808,A177994,FDA label] Mirtazapine has been shown to exert beneficial effects on sleep latency, duration, and quality due to its sedating properties.[A177967] Insomnia is a common occurrence in patients with depression, and mirtazapine has been found to be efficacious in treating this condition.[A177808]
DESCRIPTION
Potent and selective A1 antagonist
(Tocris Bioactive Compound Library)
DESCRIPTION
Potent 5-HT2 antagonist. Also 5-HT3, H1 and alpha2-antagonist. Antidepressant
(Tocriscreen Plus)
DESCRIPTION
Potent 5-HT2 antagonist. Also 5-HT3, H1 and α2-antagonist. Antidepressant
(Tocriscreen Total)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
32
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Plus
Tocriscreen Total
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
49
Molecular Weight
265.16
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
0
Rotatable Bonds
0
Ring Count
4
Aromatic Ring Count
2
cLogP
2.48
TPSA
19.37
Fraction CSP3
0.35
Chiral centers
1.0
Largest ring
7.0
QED
0.73
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Pathway
Endocrinology/Hormones
Neuroscience
GPCR/G protein
Immunology/Inflammation
Neuronal Signaling
Target
5-HT
HT
Sert (Sodium-dependent)
Adrenergic Receptor
DA transporter
dopamine
??-opioid receptor
5-HT antidepressant
5-HT Receptor
Histamine Receptor
Primary Target
Non-selective 5-HT2
MOA
Antagonist
5-HT2A Antagonists
5-HT3 Antagonists
alpha2-Adrenoceptor Antagonists
Member status
member
Therapeutic Class
Antidepressants
Source data
