Mirtazapine
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4 sources
Collated from PsychonautWiki, Pharmacology, DrugCentral, DailyMed. Where sources differ (e.g. dosing), Compare shows them side by side.
Also known as Avanza, Axit, Mirtaz, Mirtazon, Remeron, ZispinPW
Oral
Route dataPsychonautWiki
| Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| 3.5 mg | 70–130 mg | 130–190 mg | 190–250 mg | 250 mg+ |
| Onset | 15–30 minutes |
|---|---|
| Peak | 90–180 minutes |
| Offset | 2–6 hours |
| Total | 14–24 hours |
Caution / uncertainPW
🧬 Receptor activityPHDC
| Target | Action | Affinity | Source | |
|---|---|---|---|---|
| Histamine H1 receptor | — | Ki 1.6 nM | CHEMBL | TargetHistamine H1 receptor Action— AffinityKi 1.6 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2A | — | Ki 2 nM | CHEMBL | Target5-hydroxytryptamine receptor 2A Action— AffinityKi 2 nM SourceCHEMBL |
| Unchecked | — | Ki 5.1 nM | CHEMBL | TargetUnchecked Action— AffinityKi 5.1 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2C | — | Ki 5.5 nM | CHEMBL | Target5-hydroxytryptamine receptor 2C Action— AffinityKi 5.5 nM SourceCHEMBL |
| Alpha-2C adrenergic receptor | — | Ki 18 nM | CHEMBL | TargetAlpha-2C adrenergic receptor Action— AffinityKi 18 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 1A | — | Ki 18 nM | CHEMBL | Target5-hydroxytryptamine receptor 1A Action— AffinityKi 18 nM SourceCHEMBL |
| Alpha-2A adrenergic receptor | — | Ki 20 nM | CHEMBL | TargetAlpha-2A adrenergic receptor Action— AffinityKi 20 nM SourceCHEMBL |
| D(3) dopamine receptor | — | Ki 20 nM | CHEMBL | TargetD(3) dopamine receptor Action— AffinityKi 20 nM SourceCHEMBL |
| D(4) dopamine receptor | — | Ki 25 nM | CHEMBL | TargetD(4) dopamine receptor Action— AffinityKi 25 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 7 | — | Ki 265 nM | CHEMBL | Target5-hydroxytryptamine receptor 7 Action— AffinityKi 265 nM SourceCHEMBL |
| Adrenergic receptor alpha-1 | — | Ki 608 nM | CHEMBL | TargetAdrenergic receptor alpha-1 Action— AffinityKi 608 nM SourceCHEMBL |
| D(2) dopamine receptor | — | Ki 1460 nM | CHEMBL | TargetD(2) dopamine receptor Action— AffinityKi 1460 nM SourceCHEMBL |
| Norepinephrine transporter | — | Ki 1640 nM | CHEMBL | TargetNorepinephrine transporter Action— AffinityKi 1640 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 3A | — | Ki 2900 nM | CHEMBL | Target5-hydroxytryptamine receptor 3A Action— AffinityKi 2900 nM SourceCHEMBL |
| D(1A) dopamine receptor | — | Ki 4167 nM | CHEMBL | TargetD(1A) dopamine receptor Action— AffinityKi 4167 nM SourceCHEMBL |
| 5-hydroxytryptamine receptor 2A (HTR2A) | Antagonist | 7.16 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 2A (HTR2A) ActionAntagonist Affinity7.16 Ki SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 2C (HTR2C) | Antagonist | 7.41 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 2C (HTR2C) ActionAntagonist Affinity7.41 Ki SourceDRUGCENTRAL |
| Alpha-2A adrenergic receptor (ADRA2A) | Antagonist | 7.7 Ki | DRUGCENTRAL | TargetAlpha-2A adrenergic receptor (ADRA2A) ActionAntagonist Affinity7.7 Ki SourceDRUGCENTRAL |
| Alpha-2B adrenergic receptor (ADRA2B) | Antagonist | 6.65 IC50 | DRUGCENTRAL | TargetAlpha-2B adrenergic receptor (ADRA2B) ActionAntagonist Affinity6.65 IC50 SourceDRUGCENTRAL |
| Alpha-2C adrenergic receptor (ADRA2C) | Antagonist | 7.74 Ki | DRUGCENTRAL | TargetAlpha-2C adrenergic receptor (ADRA2C) ActionAntagonist Affinity7.74 Ki SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 1A (HTR1A) | — | 5.3 Kd | DRUGCENTRAL | Target5-hydroxytryptamine receptor 1A (HTR1A) Action— Affinity5.3 Kd SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 2A (Htr2a) | — | 8.7 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 2A (Htr2a) Action— Affinity8.7 Ki SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 2C (Htr2c) | — | 8.26 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 2C (Htr2c) Action— Affinity8.26 Ki SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 3A (HTR3A) | — | 5.54 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 3A (HTR3A) Action— Affinity5.54 Ki SourceDRUGCENTRAL |
| 5-hydroxytryptamine receptor 7 (HTR7) | — | 6.58 Ki | DRUGCENTRAL | Target5-hydroxytryptamine receptor 7 (HTR7) Action— Affinity6.58 Ki SourceDRUGCENTRAL |
| Adrenergic receptor alpha-1 (Adra1b) | — | 6.22 Ki | DRUGCENTRAL | TargetAdrenergic receptor alpha-1 (Adra1b) Action— Affinity6.22 Ki SourceDRUGCENTRAL |
| Alpha-1A adrenergic receptor (ADRA1A) | — | 5.5 IC50 | DRUGCENTRAL | TargetAlpha-1A adrenergic receptor (ADRA1A) Action— Affinity5.5 IC50 SourceDRUGCENTRAL |
| D(1A) dopamine receptor (DRD1) | — | 5.38 Ki | DRUGCENTRAL | TargetD(1A) dopamine receptor (DRD1) Action— Affinity5.38 Ki SourceDRUGCENTRAL |
| D(2) dopamine receptor (DRD2) | — | 5.263 Ki | DRUGCENTRAL | TargetD(2) dopamine receptor (DRD2) Action— Affinity5.263 Ki SourceDRUGCENTRAL |
| D(3) dopamine receptor (DRD3) | — | 5.24 Ki | DRUGCENTRAL | TargetD(3) dopamine receptor (DRD3) Action— Affinity5.24 Ki SourceDRUGCENTRAL |
| Histamine H1 receptor (HRH1) | — | 8.796 Ki | DRUGCENTRAL | TargetHistamine H1 receptor (HRH1) Action— Affinity8.796 Ki SourceDRUGCENTRAL |
| Muscarinic acetylcholine receptor M1 (CHRM1) | — | — | DRUGCENTRAL | TargetMuscarinic acetylcholine receptor M1 (CHRM1) Action— Affinity— SourceDRUGCENTRAL |
| Muscarinic acetylcholine receptor M2 (CHRM2) | — | — | DRUGCENTRAL | TargetMuscarinic acetylcholine receptor M2 (CHRM2) Action— Affinity— SourceDRUGCENTRAL |
| Sodium-dependent noradrenaline transporter (SLC6A2) | — | 5.337 Ki | DRUGCENTRAL | TargetSodium-dependent noradrenaline transporter (SLC6A2) Action— Affinity5.337 Ki SourceDRUGCENTRAL |
| Transporter (Slc6a2) | — | 5.79 Ki | DRUGCENTRAL | TargetTransporter (Slc6a2) Action— Affinity5.79 Ki SourceDRUGCENTRAL |
Mechanism of actionPHDM
**Summary** The mechanism of action of mirtazapine is not fully understood 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. **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, which are known to improve the symptoms of depression and form the basis of antidepressant therapy. 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 but indirectly increases 5-HT1A transmission. 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. Mirtazapine is a potent histamine (H1) receptor antagonist, which may contribute to its powerful sedating effects. The pain-relieving effects of mirtazapine may be explained by its effects on opioid receptors.
PharmacodynamicsPHDM
**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.. 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. 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. **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. 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. 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. **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. Mirtazapine has been shown to exert beneficial effects on sleep latency, duration, and quality due to its sedating properties. Insomnia is a common occurrence in patients with depression, and mirtazapine has been found to be efficacious in treating this condition.
Pharmacokinetics
Half-lifePH
20-40 hours
AbsorptionPHDM
The absorption of this drug is rapid and complete. Due to first pass metabolism in the liver and metabolism in the gut wall, absolute bioavailability is about 50%. 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. Steady-state levels are achieved by about 5 days after the initial dose. 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.
This drug is mainly excreted by the kidney. It is 75% eliminated in the urine and 15% eliminated in the feces.
The volume of distribution after an oral steady-state dose was measured to be 107 ± 42L in a pharmacokinetic study.
Total body clearance in males was found to be 31 L/h in a clinical pharmacokinetics study after intravenous administration. **Clearance in elderly patients*
Mirtazapine clearance is slower in the elderly than in younger subjects. Exercise caution when this drug is given to elderly patients. In a clinical trial, elderly males showed a marked decrease in mirtazapine clearance when compared to young males taking the same dose. This difference was less significant when clearance was compared between elderly females and younger females taking mirtazapine. **Clearance in hepatic and renal impairment** Patients with hepatic and renal impairment have decreased rates of clearance and dosage adjustments may be necessary for these patients. Moderate renal impairment and hepatic impairment cause about a 30% decrease in mirtazapine clearance. Severe renal impairment leads to a 50% decrease in mirtazapine clearance.
MetabolismPH
Mirtazapine is heavily metabolized in humans. Demethylation and hydroxylation and subsequent glucuronide conjugation are the major pathways by which mirtazapine is metabolized. 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.
Mirtazapine has known human metabolites that include 8-hydroxy-mirtazapine, N-Desmethylmirtazapine, and Mirtazapine N-oxide.
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
Protein bindingPH
Mirtazapine is about 85% bound to plasma proteins.
Plan a dose of Mirtazapine
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External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.