Loxapine

Names

[ CAS No. ]:
1977-10-2

[ Name ]:
Loxapine

[Synonym ]:
8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzoxazepine
Loxapina
Dibenzoazepine
Lossapina [DCIT]
Dibenzacepin
2-chloro-11-(4-methyl-piperazin-1-yl)-dibenzo[b,f][1,4]oxazepine
Oxilapine
Cloxazepine
2-chloro-11-(4-methyl-1-piperazinyl)dibenz[b,f][1,4]oxazepine
Loxapinum
Loxitane
Loxapin

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

[ Density]:
1.2299 (rough estimate)

[ Melting Point ]:
109-110°

[ Molecular Formula ]:
C₁₈H₁₈ClN₃O

[ Molecular Weight ]:
327.80800

[ Exact Mass ]:
327.11400

[ PSA ]:
28.07000

[ LogP ]:
3.08280

[ Vapour Pressure ]:
1.36E-08mmHg at 25°C

[ Index of Refraction ]:
1.5800 (estimate)

[ Storage condition ]:
2-8℃

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HQ4025000

CHEMICAL NAME :: Dibenz(b,f)(1,4)oxazepine, 2-chloro-11-(4-methyl-1-piperazinyl)-

CAS REGISTRY NUMBER :: 1977-10-2

LAST UPDATED :: 199612

DATA ITEMS CITED :: 19

MOLECULAR FORMULA :: C18-H18-Cl-N3-O

MOLECULAR WEIGHT :: 327.84

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

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 151 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,293,1970

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 35 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,293,1970

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 350 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,293,1970

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 18 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,293,1970

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 40 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,79,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 27 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,79,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 53 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,293,1970

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 22 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,293,1970

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >50 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,131,1970

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: >50 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Kidney, Ureter, Bladder - other changes

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,131,1970

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 50 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - miosis (pupillary constriction) Sense Organs and Special Senses (Eye) - ptosis Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,131,1970

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 100 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Behavioral - altered sleep time (including change in righting reflex) Behavioral - rigidity (including catalepsy)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,131,1970 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 960 mg/kg/30D-C

TOXIC EFFECTS :: Endocrine - changes in thymus weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,293,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 455 mg/kg/26W-C

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in bladder weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,293,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 300 mg/kg/30D-C

TOXIC EFFECTS :: Liver - changes in liver weight Blood - changes in leukocyte (WBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,293,1970 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 24 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - live birth index (measured after birth)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,305,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,305,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6 mg/kg

SEX/DURATION :: female 7-12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,305,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 24 mg/kg

SEX/DURATION :: female 7-12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,305,1970

Loxapine

Names

Biological Activity

Chemical & Physical Properties

Toxicological Information

CHEMICAL IDENTIFICATION

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds