loxapine

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1. a tranquilizer (trade name Loxitane) used to treat schizophrenia (同)Loxitane

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/23 12:05:14」(JST)

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Loxapine

Systematic (IUPAC) name
2-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine
Clinical data
Trade names	Loxapac, Loxitane, Adasuve
AHFS/Drugs.com	monograph
MedlinePlus	a682311
Licence data	EMA:Link, US Daily Med:link
Pregnancy category	US: C (Risk not ruled out)
Legal status	AU: Prescription Only (S4) US: ℞-only
Routes of administration	Inhalation, oral
Pharmacokinetic data
Protein binding	96.8%
Metabolism	Liver, extensive; active metabolites include amoxapine and 8-hydroxyloxapine. Inhibits P-glycoprotein and is a substrate of CYP1A2, CYP3A4 and CYP2D6
Half-life	Oral, 4 hours; Inhalation, 7.61 hours
Excretion	Majority are excreted within 24 hours. Main route through urine(conjugated metabolites); Small amounts through the faeces(unconjugated metabolites)
Identifiers
CAS Registry Number	1977-10-2 Y
ATC code	N05AH01
PubChem	CID 3964
IUPHAR ligand	205
DrugBank	DB00408 N
ChemSpider	3827 Y
UNII	LER583670J Y
KEGG	D02340 Y
ChEBI	CHEBI:50841 N
ChEMBL	CHEMBL831 Y
Chemical data
Formula	C18H18ClN3O
Molecular mass	327.808 g/mol
SMILES Clc2ccc1Oc4c(/N=C(\c1c2)N3CCN(C)CC3)cccc4
InChI 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  Y Key:XJGVXQDUIWGIRW-UHFFFAOYSA-N  Y
Physical data
Melting point	109 to 110 °C (228 to 230 °F)
N (what is this?)  (verify)

Loxapine is a typical antipsychotic medication, used primarily in the treatment of schizophrenia. Trade names for loxapine taken by mouth include Loxapac and Loxitane; the inhalable form is approved as Adasuve. 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.

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

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.

A brief review of loxapine 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.

Loxapine was one of five antipsychotics used in a study on the structure of neurons in parts of the brain thought to be involved in schizophrenia. Only loxapine was linked to the development of new connections between neurons.

Precautions

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

Side effects

Further information: Typical antipsychotic

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

Common side effects of loxapine (≥1% incidence) when inhaled include

• Taste sense altered (14%)
• Sedated (12%)
• Pharyngitis (3%)

Intense Sleeping (Highest Procentage) In Pill Form Blurred Speech (In Pill Form)

Common side effects of orally-administered loxapine include

• Constipation
• Dry mouth
• Akathisia
• Dizziness
• Intense Sleeping (Highest Procentage) (In Pill Form)
• Blurred Speech (In Pill Form)
• Extrapyramidal disease (dose-dependent. At lower dosages its propensity for causing extrapyramidal side effects appears to be similar to that of atypical antipsychotics
• Blurred vision
• Urinary retention
• Somnolence (which appears to be moderate in severity compared to other antipsychotic drugs)
• Dyspnoea
• Nasal congestion

Rare side effects include

• 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.

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

Synthesis

Loxapine synthesis:

References

External links

• Product monograph from Medscape (free registration required).

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 第1世代抗精神病剤：薬理学、投与、および副作用の比較 first generation antipsychotic medications pharmacology administration and comparative side effects
• 2. 統合失調症に対する薬物療法：副作用マネージメント pharmacotherapy for schizophrenia side effect management
• 3. 成人における双極性障害：急性躁病および軽躁に対する薬物療法 bipolar disorder in adults pharmacotherapy for acute mania and hypomania

English Journal

• FDA-approved drugs selected using virtual screening bind specifically to G-quadruplex DNA.

• González DC, Machado GP, Guédin A, Mergny JL, Cabrera-Pérez MA.SourceMolecular Simulation and Drug Design Group, Centre of Chemical Bioactive, Central University of Las Villas, Santa Clara 54830, Villa Clara, Cuba. daimelc@gmail.com; daimel2@uclv.edu.cu.
• Current pharmaceutical design.Curr Pharm Des.2012 Sep 24. [Epub ahead of print]
• Guanine-rich sequences found in telomeres and oncogene promoters have the ability to form G-quadruplex structures. In this paper we describe the use of a virtual screening assay to search a database of FDA-approved compounds for compounds with the potential to bind G-quadruplex DNA. More than 75
• PMID 23016840

• [Dysphagia or dysphagias during neuroleptic medication?].

• Chaumartin N, Monville M, Lachaux B.SourceUMD Henri-Colin, EPS Paul-Guiraud, 54, avenue de la République, 94800 Villejuif, France. Electronic address: nadia.chaumartin@ch-pgv.fr.
• L'Encéphale.Encephale.2012 Sep;38(4):351-5. doi: 10.1016/j.encep.2011.07.002. Epub 2011 Oct 11.
• INTRODUCTION: Dysphagia is a common symptom in the general population, and even more among psychiatric patients, but rarely seen as a sign of seriousness. It is a cause of death by suffocation, and more or less serious complications, and therefore should be diagnosed and treated. Among psychiatric p
• PMID 22980477

Japanese Journal

• Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain

• LEE T.
• Psychiatr Res 12, 277-285, 1984
• NAID 30005561263

• Tolerance phenomena with neuroleptics catalepsy, apomorphine stereoypies and striatal dopamine merabolism in the rat after single and repeated administration of loxapine and haloperidol.

• ASPER H.
• Eur. J. Pharmacol 22, 287-294, 1973
• NAID 30002516667

Related Links

• ロキサピン - d.xenowire.net

企業系リソース (薬価情報含む) ロキサピン - QLifeお薬検索 - QLife. Inc. ロキサピン - 医薬品情報・検索 イ－ファ－マ - Allied Medical Associates Co., Ltd. 管理系リソース loxapine - 規制物質法(CSA) - DEA, アメリカ合衆国 ロキサピン - 麻薬 ...

• Loxapine: MedlinePlus Drug Information - National Library of ...

Before taking loxapine, tell your doctor and pharmacist if you are allergic to loxapine or any other medications. tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional ...

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コハク酸ロキサピン loxapine succinate

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