AHFS/Drugs.com Monograph License data US FDA: Amoxapine Molar mass 313.781 g/mol Protein binding 90% | MedlinePlus a682202 CAS ID 14028-44-5 | |
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Trade names Asendin, Asendis, Defanyl, Demolox Pregnancycategory US: C (Risk not ruled out) |
What does amoxapine mean
Amoxapine (pronounced: a-mox-a-peen. Notable brand names include: Asendin, Asendis, Defanyl, Demolox. See here for more brand name information) is a tetracyclic antidepressant of the dibenzoxazepine family, though it is often classified as a secondary amine tricyclic antidepressant. It is the N-demethylated metabolite of loxapine. It first received marketing approval in the US in 1992 (approximately thirty to forty years after most of the other tricyclic antidepressants were introduced in the US).
Contents
- What does amoxapine mean
- Medical uses
- Adverse effects
- Contraindications
- Lactation
- Overdose
- Pharmacodynamics
- Pharmacokinetics
- Brand names
- References
Medical uses
Amoxapine is used in the treatment of major depressive disorder. Compared to other antidepressants it is believed to have a faster onset of action, with therapeutic effects seen within four to seven days. In excess of 80% of patients that do respond to amoxapine are reported to respond within a fortnight of the beginning of treatment. It also has properties similar to those of the atypical antipsychotics, and may behave as one and may be used in the treatment of schizophrenia off-label. Despite its apparent lack of extrapyramidal side effects in patients with schizophrenia it has been found to exacerbate motor symptoms in patients with Parkinson's disease psychosis.
Adverse effects
Adverse effects by incidence:
Note: Serious (that is, those that can either result in permanent injury or are irreversible or are potentially life-threatening) are written in bold text.
Very common (>10% incidence) adverse effects include:
Common (1-10% incidence) adverse effects include:
Uncommon/Rare (<1% incidence) adverse effects include:
Unknown incidence or relationship to drug treatment adverse effects include:
It tends to produce less anticholinergic effects, sedation and weight gain than some of the earlier tricyclic antidepressants (e.g. amitriptyline, clomipramine, doxepin, imipramine and trimipramine). It may also be less cardiotoxic than its predecessors.
Contraindications
As with all FDA-approved antidepressants it carries a black-box warning about the potential of an increase in suicidal thoughts or behaviour in children, adolescents and young adults under the age of 25. Its use is also advised against in individuals with known hypersensitivities to either amoxapine or other ingredients in its oral formulations. Its use is also recommended against in the following disease states:
Its use is also advised against in individuals concurrently on monoamine oxidase inhibitors or if they have been on one in the past 14 days and in individuals on drugs that are known to prolong the QT interval (e.g. ondansetron, citalopram, pimozide, sertindole, ziprasidone, haloperidol, chlorpromazine, thioridazine, etc.).
Lactation
Its use in breastfeeding mothers not recommended as it is excreted in breast milk and the concentration found in breast milk is approximately a quarter that of the maternal serum level.
Overdose
It is considered particularly toxic in overdose, with a high rate of renal failure (which usually takes 2–5 days), rhabdomyolysis, coma, seizures and even status epilepticus. Some believe it to be less cardiotoxic than other tricyclic antidepressants in overdose, although reports of cardiotoxic overdoses have been made.
Pharmacodynamics
Amoxapine possesses a wide array of pharmacological effects. It is a moderate and strong reuptake inhibitor of serotonin and norepinephrine, respectively, and binds to the 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, D2, α1-adrenergic, D3, D4, and H1 receptors with varying but significant affinity, where it acts as an antagonist (or inverse agonist depending on the receptor in question) at all sites. It has weak but negligible affinity for the dopamine transporter and the 5-HT1A, 5-HT1B, D1, α2-adrenergic, H4, mACh, and GABAA receptors, and no affinity for the β-adrenergic receptors or the allosteric benzodiazepine site on the GABAA receptor. Amoxapine is also a weak GlyT2 blocker, as well as a weak (Ki = 2.5 μM, EC50 = 0.98 μM) δ-opioid receptor partial agonist.
7-Hydroxyamoxapine, a major active metabolite of amoxapine, is a more potent dopamine receptor antagonist and contributes to its neuroleptic efficacy, whereas 8-hydroxyamoxapine is a norepinephrine reuptake inhibitor but a stronger serotonin reuptake inhibitor and helps to balance amoxapine's ratio of serotonin to norepinephrine transporter blockade.
The data in the following table from obtained from the PDSP Ki database.
Pharmacokinetics
Amoxapine is metabolised into two main active metabolites: 7-hydroxyamoxapine and 8-hydroxyamoxapine.
Where:
- t1/2 is the elimination half life of the compound.
- tmax is the time to peak plasma levels after oral administration of amoxapine.
- CSS is the steady state plasma concentration.
- protein binding is the extent of plasma protein binding.
- Vd is the volume of distribution of the compound.
Brand names
Brand names for amoxapine include (where † denotes discontinued brands):