Loxapine

Loxapine
Systematic (IUPAC) name
2-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682311
Pregnancy cat.  ?
Legal status  ?
Pharmacokinetic data
Metabolism Gastrointestinal, peak concn. occur between 1-2 hours.
Half-life Oral-4 hours
Excretion Majority are excreted within 24 hours. Main route through urine(conjugated metabolites); Small amounts through the faeces(unconjugated metabolites)
Identifiers
CAS number 1977-10-2 YesY
ATC code N05AH01
PubChem CID 3964
IUPHAR ligand 205
DrugBank DB00408
ChemSpider 3827 YesY
UNII LER583670J YesY
KEGG D02340 YesY
ChEBI CHEBI:50841 N
ChEMBL CHEMBL831 YesY
Chemical data
Formula C18H18ClN3O 
Mol. mass 327.808 g/mol
SMILES eMolecules & PubChem
Physical data
Melt. point 109–110 °C (228–230 °F)
 N(what is this?)  (verify)

Loxapine (Loxapac, Loxitane) is a typical antipsychotic medication, used primarily in the treatment of schizophrenia. It is a member of the dibenzoxazepine class and as a dibenzazepine derivative, it is structurally related to clozapine (which belongs to the chemically closely akin class of dibenzodiazepines). Several researchers have argued that Loxapine may behave as an atypical antipsychotic.[1]

Loxapine may be metabolized by N-demethylation to amoxapine, a tetracyclic antidepressant.[2]

Contents

Precautions

Care should be taken with consumption. At least 3 cases were reported of loxapine succinate abuse.[3]

Side effects

The most significant side-effects of loxapine are excessive salivation (hypersalivation) and indifference to surroundings. Loxapine, if administered to individuals without schizophrenia, causes emotional quieting and insensitivity. In persons with psychosis, it may control aggressive behaviour and restlessness, and reduce the severity of hallucinations and delusions. Other Side effects include tardive dyskinesia, neuroleptic malignant syndrome, extrapyramidal side effects, tremor, gynecomastia and sedation.

Dosage

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.

A brief review of loxapine[4] 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.[5]

Loxapine was one of five antipsychotics used in a study on the structure of schizophrenic neurons. Only Loxapine was linked to the development of new connections between neurons.[6]

Chemistry

Loxapine synthesis.png

Schmutz, J.; Kunzle, F.; Hunziker, F.; Gauch, R.; Helv. Chim. Acta 1967, 50, 245.

References

  1. ^ Glazer WM (1999). "Does loxapine have "atypical" properties? Clinical evidence". The Journal of Clinical Psychiatry 60 (Suppl 10): 42–6. PMID 10340686. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ "Clozapine and loxapine for schizophrenia". Drug and Therapeutics Bulletin 29 (11): 41–2. May 1991. PMID 1747161. 
  5. ^ Chakrabarti A, Bagnall A, Chue P, et al. (2007). Chakrabarti, Abhijit. ed. "Loxapine for schizophrenia". Cochrane Database of Systematic Reviews (Online) (4): CD001943. doi:10.1002/14651858.CD001943.pub2. PMID 17943763. 
  6. ^ Brennand, Kristen; Anthony Simone, Jessica Jou, Chelsea Gelboin-Burkhart, Ngoc Tran, Sarah Sangar, Yan Li, Yangling Mu, Gong Chen, Diana Yu, Shane McCarthy, Jonathan Sebat & Fred H. Gage (13 April 2011). "Modelling schizophrenia using human induced pluripotent stem cells". Nature 473 (7346): 221–5. doi:10.1038/nature09915. PMID 21490598. 

External links