Loxapine, sold under the brand names Loxitane and Adasuve (''inhalation'' only) among others, is an

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...

medication used primarily in the treatment of

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...

. The medicine is a member of the dibenzoxazepine class and structurally very similar to

clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...

. Several researchers have argued that loxapine, initially classified as a

typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics ma ...

, behaves as an

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...

. Loxapine may be metabolized by ''N''-demethylation to

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 ...

, a

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

Medical uses

The

US Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) has approved loxapine inhalation powder for the acute treatment of agitation associated with schizophrenia or

bipolar I disorder Bipolar I disorder (BD-I; pronounced "type one bipolar disorder") is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other ti ...

in adults. A brief review of loxapine found no conclusive evidence that it was particularly effective in patients with

. 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 Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. 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 antipsychotic medications. These include, e.g., gastrointestinal problems (like constipation and abdominal pain), cardiovascular problems (like tachycardia), moderate likelihood of drowsiness (relative to other antipsychotics),Taylor D, Paton C, Kapur S, Taylor D, South London and Maudsley NHS Trust. The Maudsley prescribing guidelines in psychiatry nternet Chichester, West Sussex: John Wiley & Sons; 2012 ited 2013 Sep 21 Available from: http://site.ebrary.com/lib/uqat/Doc?id=10531429 and movement problems (i.e.

extrapyramidal symptoms Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...

PS. At lower dosages its propensity for causing EPS appears to be similar to that of atypical antipsychotics.Nordstrom K. Inhaled loxapine for rapid treatment of agitation in schizophrenia and bipolar disorder: an update. Neuropsychiatry nternet 2012 Jun ited 2013 Sep 212(3):253–60. Available from: Although it is structurally similar to

, it has much lower risk of

agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...

(which, even with clozapine, is 0.8%); 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 Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylatoxins. It causes di ...

that is not thought to occur when loxapine is taken by mouth.

Pharmacology

Mechanism of action

Some authors say loxapine is a " mid-potency" typical antipsychotic. However, unlike most other typical antipsychotics, it has significant potency at the 5HT_2A receptor (6.6 nM), which is similar to atypical antipsychotics like

(5.35 nM). The higher likelihood of EPS with loxapine, compared to clozapine, may be due to its higher affinity for the D2 receptor compared to

, which has one of the lowest binding affinities at the D2 receptor of ''any'' antipsychotic.

Pharmacokinetics

Loxapine is metabolized to

, 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 In systems theory, a system or a process is in a steady state if the variables (called state variables) which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those properties '' ...

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 In mathematics, an integral assigns numbers to functions in a way that describes displacement, area, volume, and other concepts that arise by combining infinitesimal data. The process of finding integrals is called integration. Along with ...

of loxapine than when it is taken by mouth.

Chemistry

Loxapine is a dibenzoxazepine and is structurally very similar to

, an

References

External links

* {{Portal bar , Medicine Alpha-1 blockers Alpha-2 blockers Chloroarenes Dibenzoxazepines Piperazines Typical antipsychotics