What is Amoxapine?


Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCAs). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 years after most of the other TCAs were introduced in the United States).

Medical Uses

Moxapine is used in the treatment of major depressive disorder (MDD). 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 two weeks 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 and psychosis.


As with all US Food and Drug Administration (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:

  • Severe cardiovascular disorders (potential of cardiotoxic adverse effects such as QT interval prolongation).
  • Uncorrected narrow angle glaucoma.
  • Acute recovery post-myocardial infarction.

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.).


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.

Side Effects

Very Common (>10% Incidence) Adverse Effects Include:

  • Constipation.
  • Dry mouth.
  • Sedation.

Common (1–10% Incidence) Adverse Effects Include:

  • Anxiety.
  • Ataxia.
  • Blurred vision.
  • Confusion.
  • Dizziness.
  • Headache.
  • Fatigue.
  • Nausea.
  • Nervousness/restlessness.
  • Excessive appetite.
  • Rash.
  • Increased perspiration (sweating).
  • Tremor.
  • Palpitations.
  • Nightmares.
  • Excitement.
  • Weakness.
  • ECG changes.
  • Oedema.
    • An abnormal accumulation of fluids in the tissues of the body leading to swelling.
  • Prolactin levels increased.
    • Prolactin is a hormone that regulates the generation of breast milk.
    • Prolactin elevation is not as significant as with risperidone or haloperidol.

Uncommon/Rare (<1% Incidence) Adverse Effects Include:

  • Diarrhoea.
  • Flatulence.
  • Hypertension (high blood pressure).
  • Hypotension (low blood pressure).
  • Syncope (fainting).
  • Tachycardia (high heart rate).
  • Menstrual irregularity.
  • Disturbance of accommodation.
  • Mydriasis (pupil dilation).
  • Orthostatic hypotension (a drop in blood pressure that occurs upon standing up).
  • Seizure.
  • Urinary retention (being unable to pass urine).
  • Urticaria (hives).
  • Vomiting.
  • Nasal congestion.
  • Photosensitisation
  • Hypomania (a dangerously elated/irritable mood).
  • Tingling.
  • Paresthaesias of the extremities.
  • Tinnitus.
  • Disorientation.
  • Numbness.
  • Incoordination.
  • Disturbed concentration.
  • Epigastric distress.
  • Peculiar taste in the mouth.
  • Increased or decreased libido.
  • Impotence (difficulty achieving an erection).
  • Painful ejaculation.
  • Lacrimation (crying without an emotional cause).
  • Weight gain.
  • Altered liver function.
  • Breast enlargement.
  • Drug fever.
  • Pruritus (itchiness).
  • Vasculitis a disorder where blood vessels are destroyed by inflammation.
    • Can be life-threatening if it affects the right blood vessels.
  • Galactorrhoea:
    • Lactation that is not associated with pregnancy or breast feeding.
  • Delayed micturition:
    • That is, delays in urination from when a conscious effort to urinate is made.
  • Hyperthermia:
    • Elevation of body temperature; its seriousness depends on the extent of the hyperthermia.
  • Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) this is basically when the body’s level of the hormone, antidiuretic hormone, which regulates the conservation of water and the restriction of blood vessels, is elevated.
    • This is potentially fatal as it can cause electrolyte abnormalities including hyponatraemia (low blood sodium), hypokalaemia (low blood potassium) and hypocalcaemia (low blood calcium) which can be life-threatening.
  • Agranulocytosis a drop in white blood cell counts.
    • The white blood cells are the cells of the immune system that fight off foreign invaders.
    • Hence agranulocytosis leaves an individual open to life-threatening infections.
  • Leukopaenia the same as agranulocytosis but less severe.
  • Neuroleptic malignant syndrome (a potentially fatal reaction to antidopaminergic agents, most often antipsychotics.
    • It is characterised by hyperthermia, diarrhoea, tachycardia, mental status changes [e.g. confusion], rigidity, extrapyramidal side effects)
  • Tardive dyskinesia a most often irreversible neurologic reaction to antidopaminergic treatment, characterised by involuntary movements of facial muscles, tongue, lips, and other muscles.
    • It develops most often only after prolonged (months, years or even decades) exposure to antidopaminergics.
  • Extrapyramidal side effects.
    • Motor symptoms such as tremor, parkinsonism, involuntary movements, reduced ability to move one’s voluntary muscles, etc.

Unknown Incidence or Relationship to Drug Treatment Adverse Effects Include:

  • Paralytic ileus (paralysed bowel).
  • Atrial arrhythmias including atrial fibrillation.
  • Myocardial infarction (heart attack).
  • Stroke.
  • Heart block.
  • Hallucinations.
  • Purpura.
  • Petechiae.
  • Parotid swelling.
  • Changes in blood glucose levels.
  • Pancreatitis swelling of the pancreas.
  • Hepatitis swelling of the liver.
  • Urinary frequency.
  • Testicular swelling.
  • Anorexia (weight loss).
  • Alopecia (hair loss).
  • Thrombocytopenia:
    • A significant drop in platelet count that leaves one open to life-threatening bleeds.
  • Eosinophilia an elevated level of the eosinophils of the body.
    • Eosinophils are the type of immune cell that’s job is to fight off parasitic invaders.
  • Jaundice:
    • yellowing of the skin, eyes and mucous membranes due to an impaired ability of the body to clear the by product of haem breakdown, bilirubin, most often the result of liver damage as it is the liver’s responsibility to clear bilirubin.

It tends to produce less anticholinergic effects, sedation and weight gain than some of the earlier TCAs (e.g. amitriptyline, clomipramine, doxepin, imipramine, trimipramine). It may also be less cardiotoxic than its predecessors.


Refer to Tricyclic Antidepressant 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 TCAs in overdose, although reports of cardiotoxic overdoses have been made.



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


Amoxapine is metabolised into two main active metabolites: 7-hydroxyamoxapine and 8-hydroxyamoxapine.

Society and Culture

Brand Names

Brand names for amoxapine include (where † denotes discontinued brands):

  • Adisen (KR).
  • Amolife (IN).
  • Amoxan (JP).
  • Asendin† (previously marketed in CA, NZ, US).
  • Asendis† (previously marketed in IE, UK).
  • Défanyl (FR).
  • Demolox (DK†, IN, ES†).
  • Oxamine (IN).
  • Oxcap.

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What is Loxapine?


Loxapine, sold under the brand names Loxitane and Adasuve (inhalation only) among others, is a typical antipsychotic medication used primarily in the treatment of schizophrenia.

The drug is a member of the dibenzoxazepine class and structurally related to clozapine. Several researchers have argued that loxapine may behave as an atypical antipsychotic.

Loxapine may be metabolised by N-demethylation to amoxapine, a tricyclic antidepressant.

Medical Uses

The US Food and Drug Administration (FDA) has approved loxapine inhalation powder for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.

A brief review of loxapine found no conclusive evidence that it was particularly effective in patients with paranoid schizophrenia. A subsequent systematic review considered that the limited evidence did not indicate a clear difference in its effects from other antipsychotics.

Available Forms

Loxapine can be taken by mouth as a capsule or a liquid oral concentrate. It is also available as an intramuscular injection and as a powder for inhalation.

Side Effects

Loxapine can cause side effects that are generally similar to that of other medications in the typical antipsychotic class of medications. These include, e.g. gastrointestinal problems (like constipation and abdominal pain), cardiovascular problems (like tachycardia), moderate likelihood of drowsiness (relative to other antipsychotics), and movement problems (i.e. extrapyramidal symptoms (EPS)). At lower dosages its propensity for causing EPS appears to be similar to that of atypical antipsychotics. Although it is structurally similar to clozapine, it does not have the same risk of agranulocytosis (which, even with clozapine, is less than 1%); however, mild and temporary fluctuations in blood leukocyte levels can occur. Abuse of loxapine has been reported.

The inhaled formulation of loxapine carries a low risk for a type of airway adverse reaction called bronchospasm that is not thought to occur when loxapine is taken by mouth.


Mechanism of Action

Loxapine is a “mid-potency” typical antipsychotic. However, unlike most other typical antipsychotics, it has significant potency at the 5HT2A receptor (6.6 nM), which is similar to atypical antipsychotics like clozapine (5.35 nM). The higher likelihood of EPS with loxapine, compared to clozapine, may be due to its high potency for the D2 receptor.


Loxapine is metabolised to amoxapine, as well as its 8-hydroxy metabolite (8-hydroxyloxapine). Amoxapine is further metabolized to its 8-hydroxy metabolite (8-hydroxyamoxapine), which is also found in the blood of people taking loxapine. At steady-state after taking loxapine by mouth, the relative amounts of loxapine and its metabolites in the blood is as follows: 8-hydroxyloxapine > 8-hydroxyamoxapine > loxapine.

The pharmacokinetics of loxapine change depending on how it is given. Intramuscular injections of loxapine lead to higher blood levels and area under the curve of loxapine than when it is taken by mouth.


Loxapine is a dibenzoxazepine and is structurally related to clozapine.