Loxapine
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| Clinical data | |
|---|---|
| Trade names | Several trade names worldwide[1] |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682311 |
| License data | |
| Pregnancy category |
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| Routes of administration | Oral, powder for inhalation |
| ATC code | N05AH01 (WHO) |
| 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" /> |
| 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  |
| PubChem (CID) | 3964 |
| IUPHAR/BPS | 205 |
| DrugBank |
DB00408  |
| ChemSpider |
3827 |
| UNII |
LER583670J |
| KEGG |
D02340 |
| ChEBI |
CHEBI:50841 |
| ChEMBL |
CHEMBL831 |
| ECHA InfoCard | 100.016.215 |
| Chemical and physical data | |
| Formula | C18H18ClN3O |
| Molar mass | 327.808 g/mol |
| 3D model (Jmol) | Interactive image |
| Melting point | 109 to 110 °C (228 to 230 °F) |
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| (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
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]
- Paralytic ileus
- Agranulocytosis
- Leukopenia
- Thrombocytopenia
- Hepatocellular liver damage
- Neuroleptic malignant syndrome
- Seizure
- Tardive dyskinesia
- Stroke
- Transient ischaemic attack
- Death
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 2 Drugs.com International names for loxapine Page accessed March 3, 2016
- 1 2 3 4 5 6 Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 21]. Greenwood Village, CO: Thomsen Healthcare; 2013.
- ↑ Glazer WM (1999). "Does loxapine have "atypical" properties? Clinical evidence". The Journal of Clinical Psychiatry. 60 (Suppl 10): 42–6. PMID 10340686.
- ↑ 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.
- ↑ Harrison, Pam: Inhalant Approved for Agitation in Bipolar I, Schizophrenia. Medscape. Dec 24, 2012.
- ↑ "Clozapine and loxapine for schizophrenia". Drug and Therapeutics Bulletin. 29 (11): 41–2. May 1991. PMID 1747161.
- ↑ 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.
- ↑ 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.
- ↑ 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
- ↑ 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
- ↑ 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
- Product monograph from Medscape (free registration required).