Loxapine

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Loxapine
Loxapine.svg
Loxapine ball-and-stick model.png
Systematic (IUPAC) name
8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzoxazepine
Clinical data
Trade names Several trade names worldwide[1]
AHFS/Drugs.com monograph
MedlinePlus a682311
Licence data EMA:Link, US Daily Med:link
Pregnancy
category
  • US: C (Risk not ruled out)
Legal status
Routes of
administration		 Oral, powder for inhalation
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" />
Biological 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 1977-10-2 YesY
ATC code N05AH01 (WHO)
PubChem CID: 3964
IUPHAR/BPS 205
DrugBank DB00408 N
ChemSpider 3827 YesY
UNII LER583670J YesY
KEGG D02340 YesY
ChEBI CHEBI:50841 N
ChEMBL CHEMBL831 YesY
Chemical data
Formula C18H18ClN3O
Molecular mass 327.808 g/mol
  • Clc2ccc1Oc4c(/N=C(\c1c2)N3CCN(C)CC3)cccc4
  • InChI=1S/C18H18ClN3O/c1-21-8-10-22(11-9-21)18-14-12-13(19)6-7-16(14)23-17-5-3-2-4-15(17)20-18/h2-7,12H,8-11H2,1H3 YesY
  • Key:XJGVXQDUIWGIRW-UHFFFAOYSA-N YesY
Physical data
Melting point 109 to 110 °C (228 to 230 °F)
 NYesY (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]

Therapeutic uses and dosages

The typical starting dosage is 10 mg twice daily; usual dose range 30–50 mg twice daily; maximum recommended dosage is 250 mg per day. The US Food and Drug Administration (FDA) has approved loxapine inhalation powder 10 mg (Adasuve, Alexza Pharmaceuticals) for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.[5]

A brief review of loxapine[6] 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.[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

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Further information: Typical antipsychotic

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 (Highest Percentage)
  • Blurred Speech
  • Extrapyramidal disease (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

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

Molecular target Binding affinity (Ki [nM]) for loxapine Binding affinity (Ki [nM]) for amoxapine
5-HT1A 2456 -
5-HT1B 388 -
5-HT1D 3468 -
5-HT1E 1399 -
5-HT2A 6.63 0.5
5-HT2C 13.3 2 (Cloned rat receptor protein)
5-HT3 190 -
5-HT5A 776 -
5-HT6 31.0 50
5-HT7 87.6 40.2 (Rat, Cloned)
α1A 31 -
α1B 53 -
α2A 150.9 -
α2B 107.8 -
α2C 80.0 -
β1 >10000 -
β1 >10000 -
M1 119.5 -
M2 445 -
M3 211.3 -
M4 1266 -
M5 166 -
D1 54 -
D2 11 20.8
D3 19.33 21
D4 8.4 21
D5 75 -
H1 4.9 -
H2 208 -
H4 5048 -
SERT >10000 58
NET 5698 16
DAT >10000 58

See also

References

  1. ↑ 1.0 1.1 Drugs.com International names for loxapine Page accessed March 3, 2016
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 21]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Harrison, Pam: Inhalant Approved for Agitation in Bipolar I, Schizophrenia. Medscape. Dec 24, 2012.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  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: http://www.futuremedicine.com/doi/abs/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: http://site.ebrary.com/lib/uqat/Doc?id=10531429
  11. ↑ National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Aug 3]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php

External links

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