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Loxapine

Loxapine
Loxapine.svg
Loxapine ball-and-stick model.png
Clinical data
Trade names Several trade names worldwide[1]
AHFS/Drugs.com Monograph
MedlinePlus a682311
License data
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Oral, powder for inhalation
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 96.8%[2]
Metabolism Extensive hepatic; active metabolites include amoxapine and 8-hydroxyloxapine. Inhibits P-gp and is a substrate of CYP1A2, CYP3A4 and CYP2D6<re name = "DrugPoint" />
Elimination half-life 4 hours (oral); 7.61 hours (inhalation) [2]
Excretion Majority are excreted within 24 hours, main route through urine (conjugated metabolites), small amounts through the feces (unconjugated metabolites)
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.016.215 Edit this at Wikidata
Chemical and physical data
Formula C18H18ClN3O
Molar mass 327.808 g/mol
3D model (JSmol)
Melting point 109 to 110 °C (228 to 230 °F)
 ☒N☑Y (what is this?)  (verify)

Loxapine (several trade names worldwide[1]) 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 (which belongs to the chemically akin class of dibenzodiazepines). Several researchers have argued that loxapine may behave as an atypical antipsychotic.[3]

Loxapine may be metabolized by N-demethylation to amoxapine, a tetracyclic antidepressant.[4]

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.[5]

A brief review of loxapine found no conclusive evidence that it was particularly effective in patients with paranoid schizophrenia.[6] A subsequent systematic review considered that the limited evidence did not indicate a clear difference in its effects from other antipsychotics.[7]

Precautions

This drug is unrelated to the habit-forming benzodiazepines, and misuse is rare.[8] The risks and side effect profile are comparable to other antipsychotics.

Side effects

Note: Percentages given after possible adverse effects refer to the incidence of said adverse effects, according to DrugPoint.[2]

Common side effects of loxapine (≥1% incidence) when inhaled include
[2]
  • Taste sense altered (14%)
  • Sedated (12%)
  • Pharyngitis (3%)
Common side effects of orally-administered loxapine include
[2]
  • Constipation
  • Dry mouth
  • Akathisia
  • Dizziness
  • Intense sleeping
  • Slurred speech
  • Extrapyramidal symptoms (dose-dependent. At lower dosages its propensity for causing extrapyramidal side effects appears to be similar to that of atypical antipsychotics[9]
  • Blurred vision
  • Urinary retention
  • Somnolence (which appears to be moderate in severity compared to other antipsychotic drugs[10])
  • Dyspnoea
  • Nasal congestion
Rare side effects include
[2]

Pharmacology

Loxapine (and metabolite)[11][12]
Site LOX AMX
5-HT1A 2,460 ND
5-HT1B 388 ND
5-HT1D 3,470 ND
5-HT1E 1,400 ND
5-HT2A 6.6 0.5
5-HT2C 13 2 (rat)
5-HT3 190 ND
5-HT5A 780 ND
5-HT6 31 50
5-HT7 88 40 (rat)
α1A 31 ND
α1B 53 ND
α2A 151 ND
α2B 108 ND
α2C 80 ND
β1 >10,000 ND
β2 >10,000 ND
M1 120 ND
M2 445 ND
M3 211 ND
M4 1,270 ND
M5 166 ND
D1 54 ND
D2 11 21
D3 19 21
D4 8.4 21
D5 75 ND
H1 2.2–4.9 7.9–25
H2 208 ND
H3 55,000 >100,000
H4 5,050–8,710 6,310
SERT >10,000 58
NET 5,700 16
DAT >10,000 58
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

The data in the table to the right was obtained from the PDSP Ki database and they are for binding towards human cloned proteins (receptor and transporter) unless otherwise specified.[11]

See also

References

  1. ^ a b Drugs.com International names for loxapine Page accessed March 3, 2016
  2. ^ a b c d e f Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 21]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  3. ^ Glazer WM (1999). "Does loxapine have "atypical" properties? Clinical evidence". The Journal of Clinical Psychiatry. 60 (Suppl 10): 42–6. PMID 10340686.
  4. ^ Cheung SW, Tang SW, Remington G (March 1991). "Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography". Journal of Chromatography. 564 (1): 213–21. doi:10.1016/0378-4347(91)80083-O. PMID 1860915.
  5. ^ Harrison, Pam: Inhalant Approved for Agitation in Bipolar I, Schizophrenia. Medscape. Dec 24, 2012.
  6. ^ "Clozapine and loxapine for schizophrenia". Drug and Therapeutics Bulletin. 29 (11): 41–2. May 1991. PMID 1747161.
  7. ^ Chakrabarti A, Bagnall A, Chue P, et al. (2007). Chakrabarti A, ed. "Loxapine for schizophrenia". Cochrane Database of Systematic Reviews (4): CD001943. doi:10.1002/14651858.CD001943.pub2. PMID 17943763.
  8. ^ Sperry L, Hudson B, Chan CH (March 1984). "Loxapine abuse". The New England Journal of Medicine. 310 (9): 598. doi:10.1056/NEJM198403013100920. PMID 6694719.
  9. ^ Nordstrom K. Inhaled loxapine for rapid treatment of agitation in schizophrenia and bipolar disorder: an update. Neuropsychiatry [Internet]. 2012 Jun [cited 2013 Sep 21];2(3):253–60. Available from: Nordstrom, Kimberly (2012). "Archived copy". Neuropsychiatry. 2 (3): 253–260. doi:10.2217/npy.12.23.
  10. ^ Taylor D, Paton C, Kapur S, Taylor D, South London and Maudsley NHS Trust. The Maudsley prescribing guidelines in psychiatry [Internet]. Chichester, West Sussex: John Wiley & Sons; 2012 [cited 2013 Sep 21]. Available from: [site.ebrary.com]
  11. ^ a b Roth, BL; Driscol, J. "PDSP Ki Database" (HTML). Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  12. ^ Appl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R (2012). "Interactions of recombinant human histamine H₁R, H₂R, H₃R, and H₄R receptors with 34 antidepressants and antipsychotics". Naunyn Schmiedebergs Arch. Pharmacol. 385 (2): 145–70. doi:10.1007/s00210-011-0704-0. PMID 22033803.

External links