Loxapine

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 schizophrenia.{{cite journal | vauthors = | title = Clozapine and loxapine for schizophrenia | journal = Drug and Therapeutics Bulletin | volume = 29 | issue = 11 | pages = 41–42 | date = May 1991 | pmid = 1747161 | doi = 10.1136/dtb.29.11.41 | s2cid = 27613339 }} A subsequent systematic review considered that the limited evidence did not indicate a clear difference in its effects from other antipsychotics.{{cite journal | vauthors = Chakrabarti A, Bagnall A, Chue P, Fenton M, Palaniswamy V, Wong W, Xia J | title = Loxapine for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 2007 | issue = 4 | pages = CD001943 | date = October 2007 | pmid = 17943763 | pmc = 7017975 | doi = 10.1002/14651858.CD001943.pub2 | veditors = Chakrabarti A }}

Loxapine can be taken by mouth.{{cite web |title=LOXITANE Package Insert |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017525s051,017658s038,018039s024lbl.pdf |publisher=Watson Laboratories, Inc.}} It is also available as an intramuscular injection and as a powder for inhalation.

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),{{cite book | vauthors = Taylor D, Paton C, Kapur S, Taylor D |title=The Maudsley prescribing guidelines in psychiatry |date=2012 |location=Chichester, West Sussex | publisher = Wiley-Blackwell |isbn=978-0-470-97948-8 |edition=11th}} and movement problems (i.e. extrapyramidal symptoms [EPS]).{{cite journal | vauthors = Chakrabarti A, Bagnall A, Chue P, Fenton M, Palaniswamy V, Wong W, Xia J | title = Loxapine for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 2007 | issue = 4 | pages = CD001943 | date = October 2007 | pmid = 17943763 | pmc = 7017975 | doi = 10.1002/14651858.CD001943.pub2 }} At lower dosages its propensity for causing EPS appears to be similar to that of atypical antipsychotics.{{Cite journal|journal=Neuropsychiatry |volume=2 |issue=3 |pages=253–260 |doi=10.2217/npy.12.23 |year=2012 | vauthors = Nordstrom K |title=Inhaled loxapine for rapid treatment of agitation in schizophrenia and bipolar disorder: An update |s2cid=39718567 }} Although it is structurally similar to clozapine, it has much lower risk of agranulocytosis (which, even with clozapine, is 0.8%); however, mild and temporary fluctuations in blood leukocyte levels can occur.{{cite journal | vauthors = DePaulo JR, Ayd FJ | title = Loxapine: fifteen years' clinical experience | journal = Psychosomatics | volume = 23 | issue = 3 | pages = 261–271 | date = March 1982 | pmid = 7041162 | doi = 10.1016/S0033-3182(82)73416-4 }}{{cite journal | vauthors = Singh AN, Barlas C, Singh S, Franks P, Mishra RK | title = A neurochemical basis for the antipsychotic activity of loxapine: interactions with dopamine D1, D2, D4 and serotonin 5-HT2 receptor subtypes | journal = Journal of Psychiatry & Neuroscience | volume = 21 | issue = 1 | pages = 29–35 | date = January 1996 | pmid = 8580115 | pmc = 1188731 }} Abuse of loxapine has been reported.{{cite journal | vauthors = Sperry L, Hudson B, Chan CH | title = Loxapine abuse | journal = The New England Journal of Medicine | volume = 310 | issue = 9 | pages = 598 | date = March 1984 | pmid = 6694719 | doi = 10.1056/NEJM198403013100920 }}

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.{{cite web |title=ADASUVE Package Insert |url=https://www.adasuve.com/PDF/AdasuvePI.pdf |publisher=Galen US Inc}}

Some scientists 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 clozapine (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 clozapine, which has one of the lowest binding affinities at the D2 receptor of any antipsychotic.

Loxapine is metabolized 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.{{cite journal | vauthors = Simpson GM, Cooper TB, Lee JH, Young MA | title = Clinical and plasma level characteristics of intramuscular and oral loxapine | journal = Psychopharmacology | volume = 56 | issue = 2 | pages = 225–232 | date = March 1978 | pmid = 417377 | doi = 10.1007/BF00431855 | s2cid = 21795809 }} 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 very similar to clozapine, an atypical antipsychotic.

File:Loxapine and clozapine.svg

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• {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/loxapine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Loxapine }}

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