Banner
targets (4)
for drugs
Identification
Name Loxapine
Accession Number DB00408 (APRD00574)
Type small molecule
Groups approved
Description

An antipsychotic agent used in schizophrenia. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Cloxazepine
  • Dibenzacepin
  • Dibenzoazepine
  • Hydrofluoride 3170
  • Lossapina [Dcit]
  • Loxapac
  • Loxapin
  • Loxapina [INN-Spanish]
  • Loxapine [Usan:Ban:Inn]
  • Loxapinum [INN-Latin]
  • Loxepine
  • Loxitane C
  • Loxitane Im
  • Oxilapine
Brand name mixtures Not Available
Categories
  • Antipsychotics
  • Dopamine Antagonists
  • Antipsychotic Agents
CAS number 1977-10-2
Weight Average: 327.808
Monoisotopic: 327.113839920
Chemical Formula C18H18ClN3O
InChI Key InChIKey=XJGVXQDUIWGIRW-UHFFFAOYSA-N
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
Plain Text
IUPAC Name
13-chloro-10-(4-methylpiperazin-1-yl)-2-oxa-9-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene
SMILES
CN1CCN(CC1)C1=NC2=C(OC3=C1C=C(Cl)C=C3)C=CC=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzoxazepines
Substructures
  • Carboxylic Acids and Derivatives
  • Phenols and Derivatives
  • Piperazines
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Aliphatic and Aryl Amines
  • Benzoxazepines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamidines
  • Anisoles
  • Imines
  • Phenyl Esters
  • Anilines
Pharmacology
Indication For the management of the manifestations of psychotic disorders such as schizophrenia
Pharmacodynamics Loxapine, a dibenzoxazepine compound, represents a subclass of tricyclic antipsychotic agents, chemically distinct from the thioxanthenes, butyrophenones, and phenothiazines. Pharmacologically, Loxapine is a tranquilizer for which the exact mode of action has not been established, however, it is believed that by antagonising dopamine and serotonin receptors, there is a marked cortical inhibition which can manifest as tranquilization and suppression of aggression.
Mechanism of action Loxapine is a dopamine antagonist, and also a serotonin 5-HT2 blocker. The exact mode of action of Loxapine has not been established, however changes in the level of excitability of subcortical inhibitory areas have been observed in several animal species in association with such manifestations of tranquilization as calming effects and suppression of aggressive behavior.
Absorption Systemic bioavailability of the parent drug was only about one third that after an equivalent intramuscular dose (25 mg base) in male volunteers
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic
Route of elimination Metabolites are excreted in the urine in the form of conjugates and in the feces unconjugated.
Half life Oral-4 hours
Clearance Not Available
Toxicity LD50=65 mg/kg (Orally in mice)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Watson laboratories inc
  • Actavis totowa llc
  • Mylan pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Liquid Intramuscular
Solution Oral
Tablet Oral
Prices
Unit description Cost Unit
Loxapac 50 mg/ml 7.05 USD ml
Loxitane 50 mg capsule 4.04 USD capsule
Loxitane 25 mg capsule 3.09 USD capsule
Loxapine 50 mg capsule 2.57 USD capsule
Loxitane 10 mg capsule 2.04 USD capsule
Loxapine 25 mg capsule 1.92 USD capsule
Loxitane 5 mg capsule 1.58 USD capsule
Loxapine 10 mg capsule 1.27 USD capsule
Loxapine Succinate 5 mg capsule 1.03 USD capsule
Loxapine 5 mg capsule 0.99 USD capsule
Pms-Loxapine 50 mg Tablet 0.54 USD tablet
Pms-Loxapine 25 mg Tablet 0.41 USD tablet
Pms-Loxapine 10 mg Tablet 0.26 USD tablet
Pms-Loxapine 5 mg Tablet 0.16 USD tablet
Pms-Loxapine 2.5 mg Tablet 0.08 USD tablet
Patents Not Available
Properties
State solid
Melting point 109-110 oC
Experimental Properties
Property Value Source
logP 3.6 PhysProp
Predicted Properties
Property Value Source
water solubility 1.03e-01 g/l ALOGPS
logP 3.18 ALOGPS
logP 3.46 ChemAxon Molconvert
logS -3.50 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 28.07 ChemAxon Molconvert
rotatable bond count 0 ChemAxon Molconvert
refractivity 95.11 ChemAxon Molconvert
polarizability 34.99 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Glazer WM: Does loxapine have “atypical” properties? Clinical evidence. J Clin Psychiatry. 1999;60 Suppl 10:42-6. Pubmed
  2. Cheung SW, Tang SW, Remington G: Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography. J Chromatogr. 1991 Mar 8;564(1):213-21. Pubmed
External Links
Resource Link
KEGG Drug D02340 Link_out
KEGG Compound C07104 Link_out
PubChem Compound 3964 Link_out
PubChem Substance 46505047 Link_out
ChemSpider 3827 Link_out
BindingDB 22871 Link_out
ChEBI 50841 Link_out
ChEMBL 50841 Link_out
Therapeutic Targets Database DAP000311 Link_out
PharmGKB PA450273 Link_out
Drug Product Database 2255448 Link_out
RxList http://www.rxlist.com/cgi/generic2/loxapineoc.htm Link_out
Drugs.com http://www.drugs.com/cdi/loxapine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Loxapine Link_out
ATC Codes
  • N05AH01
AHFS Codes
  • 28:16.08.92
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food to reduce irritation. Avoid alcohol.
Targets

1. D(2) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lee T, Tang SW: Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain. Psychiatry Res. 1984 Aug;12(4):277-85. Pubmed
  2. Hjerde E, Dahl SG, Sylte I: Atypical and typical antipsychotic drug interactions with the dopamine D2 receptor. Eur J Med Chem. 2005 Feb;40(2):185-94. Pubmed
  3. Kalkman HO, Neumann V, Nozulak J, Tricklebank MD: Cataleptogenic effect of subtype selective 5-HT receptor antagonists in the rat. Eur J Pharmacol. 1998 Feb 19;343(2-3):201-7. Pubmed
  4. Froimowitz M, Cody V: Biologically active conformers of phenothiazines and thioxanthenes. Further evidence for a ligand model of dopamine D2 receptor antagonists. J Med Chem. 1993 Jul 23;36(15):2219-27. Pubmed
  5. Froimowitz M, Cody V: The incorporation of butyrophenones and related compounds into a pharmacophore for dopamine D2 antagonists. Drug Des Discov. 1997 Aug;15(2):63-81. Pubmed
  6. Lang AE, Sandor P, Duff J: Remoxipride in Parkinson’s disease: differential response in patients with dyskinesias fluctuations versus psychosis. Clin Neuropharmacol. 1995 Feb;18(1):39-45. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. D(1A) dopamine receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21728 Link_out
Gene: DRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. 5-hydroxytryptamine 2A receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Li Z, Ichikawa J, Meltzer HY: A comparison of the effects of loxapine with ziprasidone and thioridazine on the release of dopamine and acetylcholine in the prefrontal cortex and nucleus accumbens. Psychopharmacology (Berl). 2003 May;167(3):315-23. Epub 2003 Mar 28. Pubmed

4. 5-hydroxytryptamine 2C receptor

Pharmacological action: unknown
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Herrick-Davis K, Grinde E, Teitler M: Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. J Pharmacol Exp Ther. 2000 Oct;295(1):226-32. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:03

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.