Loxapine succinate

Names

[ Name ]:
Loxapine succinate

[Synonym ]:
2-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine succinate (1:1)
Succinic acid - 2-chloro-11-(4-methyl-1-piperazinyl)dibenzo[b,f][1,4]oxazepine (1:1)
Daxolin
Butandisäure--2-chlor-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepin(1:1)
loxapine succinate salt
acide butanedioïque - 2-chloro-11-(4-méthylpipérazin-1-yl)dibenzo[b,f][1,4]oxazépine (1:1)
MFCD00069298
Loxitane
Cloxazepin
Dibenz[b,f][1,4]oxazepine, 2-chloro-11-(4-methyl-1-piperazinyl)-, butanedioate (1:1)
Loxapac
EINECS 248-682-0
butanedioic acid,8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzoxazepine
2-chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine butanedioate
Lederle
2-Chloro-11-(4-methyl-1-piperazinyl)dibenzo[b,f][1,4]oxazepine succinate
Loxapine succinate
Loxapine (succinate)

Biological Activity

[Description]:

Loxapine Succinate is a D2DR and D4DR inhibitor, serotonergic receptor antagonist and also a dibenzoxazepine anti-psychotic agent.IC50 value: Target: D2DR/D4DR; 5-HT receptorin vitro: In the presence of Loxapine, [3H]ketanserin binds to 5-HT2 receptor in Frontal cortex of brain in human and bovine with ki value of 6.2 nM and 6.6 nM, respectively. Loxapine has the rank order of potency for the various receptors appears to be as follows:5-HT2≥D4>>>D1>D2 in comparing competition experiments involving the human membranes [1]. Loxapine 0.2 μM, 2 μM and 20 μM reduces IL-1beta secretion by LPS-activated mixed glia cultures after 1 and 3 days of exposure. Loxapine in concentrations of 0.2 μM, 2 μM and 20 μM reduces IL-2 secretion in mixed glia cultures after 1 and 3 days of exposure, and additionally Loxapine decreases IL-1beta and IL-2 secretion in LPS-induced microglia cultures in concentrations of 2 μM, 10 μM and 20 μM [2].in vivo: Loxapine (5 mg/kg) induces a very significant reduction (more than 50%) of serotonin (S2) receptor density after 4 weeks or 10 weeks of daily injection in the rat. Loxapine (5 mg/kg) does not change dopamine receptor density but greatly reduces serotonin receptor density by 47% in the brain of rats [3].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

Research Areas >> Neurological Disease

[References]

[1]. Singh AN, et al. A neurochemical basis for the antipsychotic activity of loxapine: interactions with dopamine D1, D2, D4 and serotonin 5-HT2 receptor subtypes. J Psychiatry Neurosci. 1996 Jan;21(1):29-35.

[2]. Labuzek K, et al. Chlorpromazine and loxapine reduce interleukin-1beta and interleukin-2 release by rat mixed glial and microglial cell cultures. Eur Neuropsychopharmacol. 2005 Jan;15(1):23-30.

[3]. Lee T, et al. 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.

[4]. Kalkman HO, et al. Clozapine inhibits catalepsy induced by olanzapine and loxapine, but prolongs catalepsy induced by SCH 23390 in rats. Naunyn Schmiedebergs Arch Pharmacol. 1997 Mar;355(3):361-4.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
458.6ºC at 760mmHg

[ Melting Point ]:
150-152°C

[ Molecular Formula ]:
C₂₂H₂₄ClN₃O₅

[ Molecular Weight ]:
445.896

[ Flash Point ]:
231.1ºC

[ Exact Mass ]:
445.140442

[ PSA ]:
102.67000

[ LogP ]:
3.01860

[ Storage condition ]:
-20°C Freezer

[ Water Solubility ]:
H2O: soluble

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: WM5750000

CAS REGISTRY NUMBER :: 27833-64-3

LAST UPDATED :: 198910

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C18-H18-Cl-N3-O.C4-H6-O4

MOLECULAR WEIGHT :: 445.94

WISWESSER LINE NOTATION :: T C676 BO INJ MG J- AT6N DNTJ D1 &QV2VQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 6 mg/kg/2D-I

TOXIC EFFECTS :: Behavioral - toxic psychosis

REFERENCE :: JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 44,37,1983

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 30 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - coma Lungs, Thorax, or Respiration - chronic pulmonary edema

REFERENCE :: CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 14,181,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 27 mg/kg/9D-I

TOXIC EFFECTS :: Endocrine - hyperglycemia

REFERENCE :: JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 44,347,1983

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
Xi

[ RIDADR ]:
UN 2811 6.1 / PGII

[ WGK Germany ]:
3

[ RTECS ]:
WM5750000

Articles

Investigation of the disposition of loxapine, amoxapine and their hydroxylated metabolites in different brain regions, CSF and plasma of rat by LC–MS/MS

J. Pharm. Biomed. Anal. 58 , 83-93, (2012)

Loxapine represents an interesting example of old “new” drug and is recently drawing attention for its novel inhalation formulation for the treatment of both psychiatric and non-psychiatric disorders....

In vitro aerosol characterization of Staccato(®) Loxapine.

Int. J. Pharm. 403(1-2) , 101-8, (2011)

Medicinal aerosol products (metered dose and dry powder inhalers) require characterization testing over a wide range of use and pre-operating stress scenarios in order to ensure robust product perform...

Inhaled loxapine for agitation revisited: focus on effect sizes from 2 Phase III randomised controlled trials in persons with schizophrenia or bipolar disorder.

Int. J. Clin. Pract. 66(3) , 318-25, (2012)

To describe the efficacy of inhaled loxapine for the treatment of agitation associated with schizophrenia or bipolar disorder using different examples of effect size (ES).Psychopharmacologic Drug Advi...

Related Compounds

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