| Candidate ID: | R0101 |
| Source ID: | DB00370 |
| Source Type: | approved |
| Compound Type: |
small molecule
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| Compound Name: |
Mirtazapine
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| Synonyms: |
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| Molecular Formula: |
C17H19N3
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| SMILES: |
CN1CCN2C(C1)C1=CC=CC=C1CC1=C2N=CC=C1
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| Structure: |
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| DrugBank Description: |
Mirtazapine is a tetracyclic _piperazino-azepine_ antidepressant agent that was initially approved for the treatment of major depressive disorder (MDD) in the Netherlands in 1994.[A177946] This drug was first manufactured by Organon Inc., and received FDA approval in 1997 for the treatment of major depressive disorder.[T595, L6157] The effects of this drug may be observed as early as 1 week after beginning therapy.[A178144,L6160]
In addition to its beneficial effects in depression, mirtazapine has been reported to be efficacious in the off-label management of various other conditions. It may improve the symptoms of neurological disorders, reverse weight loss caused by medical conditions, improve sleep, and prevent nausea and vomiting after surgery.[A177811]
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| CAS Number: |
85650-52-8
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| Molecular Weight: |
265.3529
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| DrugBank 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]
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| DrugBank Pharmacology: |
**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]
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| DrugBank 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]
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| Targets: |
5-hydroxytryptamine receptor 2A; 5HT3 serotonin receptor; Alpha-2A adrenergic receptor; Alpha-1 adrenergic receptors; 5-hydroxytryptamine receptor 2C; Kappa-type opioid receptor; Histamine H1 receptor
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| Inclusion Criteria: |
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