Amisulpride

Names

[ Name ]:
Amisulpride

[Synonym ]:
Amisulpiride
Aminosultopride
Socian
Benzamide, 4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxy-
4-Amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide
Amisulpride
4-amino-N-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-2-methoxybenzamide
Amisulpridum [INN-Latin]
amisulpridum
4-amino-N-[(1-ethyl-2-pyrrolidin-yl)methyl]-5-(ethyl-sulfonyl)-2--methoxybenzamide
MFCD00866691
Deniban
EINECS 275-831-7
Solian
UNII:8110R61I4U
4-Amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-o-anisamide
amisulprida
4-amino-N-[(1-ethylpyrrolidin-2-yl)methyl]-5-(ethylsulfonyl)-2-methoxybenzamide

Biological Activity

[Description]:

Amisulpride is a dopamine D2/D3 receptor antagonist with Kis of 2.8 and 3.2 nM for human dopamine D2 and D3, respectively.

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

Research Areas >> Cancer

[Target]

Ki: 2.8 nM (D2 receptor), 3.2 nM (D3 receptor)[1]

[In Vitro]

Amisulpride is an atypical dopamine D2/D3 receptor antagonist with Kis of 2.8 and 3.2 nM for human dopamine D2 and D3, respectively. Amisulpride (100 nM) inhibits quinpirole-elicited [3H]thymidine incorporation with an IC50 value of 22±3 nM (n=3). Amisulpride slightly but significantly increases [3H]dopamine release from slices of the rat striatum (S2/S1=0.88±0.04 under control conditions, n=6; 1.04±0.08 in the presence of 100 nM Amisulpride,n=4; P<0.05) and opposes the inhibitory effects of 7-OH-DPAT in both brain areas[1].

[In Vivo]

Only the highest dose of Amisulpride (100 mg/kg) significantly reduces dopamine levels in the striatum or limbic system. Amisulpride significantly increases the synthesis of dopamine in the rat striatum and limbic system at doses of 20 and 100 mg/kg. Amisulpride (0.5 to 75 mg/kg) fails to provoke an additional increase in dopa accumulation in the striatum but slightly accelerates, at 75 mg/kg, dopamine synthesis in the limbic system. In comparison with vehicle-treated controls, Amisulpride (10 mg/kg) increases extracellular dopamine levels. The administration of Amisulpride (0.5 to 15 mg/kg s.c.) provokes a time- and dose-dependent increase in the stimulation-evoked dopamine release. Amisulpride decreases striatal ACh levels significantly at 30 and 100 mg/kg (87.5% and 56.3% of control levels, respectively)[1]. In both acute study, Amisulpride (70 mg/kg, p.o.) significantly increases the duration of swimming behavior [F(3,28)=45.90, p<0.01][2].

[Cell Assay]

The functional effects of Amisulpride at the dopamine D3 receptor subtype are assessed. Briefly, the mitogenic response elicited in NG108-15 neuroblastoma-glioma cells stably transfected with human dopamine D3 receptor cDNA by the addition of 10 nM quinpirole in the presence of 1 μM forskolin is quantified by the incorporation of [3H]thymidine. Antagonism of quinpirole-induced mitogenesis is measured in the presence of increasing (0.1 to 100 nM) concentrations of Amisulpride[1].

[Animal admin]

A total of 64 male Swiss albino mice weighing between 20 to 30 g are used. The animals are fed with standard pellet diet and water ad libitum. The mice are divided in different groups (n=8 in each group) and drug administration is done as follows: Group 1 (control): distilled water (1 mL/kg) 23.5, 5 and 1 h before the test. Group 3 (Amisulpride): Amisulpride (70 mg/kg) 23.5, 5 and 1 h before the test[2].

[References]

[1]. Schoemaker H, et al. Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity. J Pharmacol Exp Ther. 1997 Jan;280(1):83-97.

[2]. Pawar GR, et al. Evaluation of antidepressant like property of amisulpride per se and its comparison with fluoxetine and olanzapine using forced swimming test in albino mice. Acta Pol Pharm. 2009 May-Jun;66(3):327-31.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
558.9±50.0 °C at 760 mmHg

[ Melting Point ]:
124-128ºC

[ Molecular Formula ]:
C₁₇H₂₇N₃O₄S

[ Molecular Weight ]:
369.479

[ Flash Point ]:
291.8±30.1 °C

[ Exact Mass ]:
369.172241

[ PSA ]:
110.11000

[ LogP ]:
1.60

[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C

[ Index of Refraction ]:
1.546

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: ≥5 mg/mL

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: CV2308701

CHEMICAL NAME :: Benzamide, 4-amino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsu lfonyl)-2-methoxy-

CAS REGISTRY NUMBER :: 71675-85-9

LAST UPDATED :: 199201

DATA ITEMS CITED :: 4

MOLECULAR FORMULA :: C17-H27-N3-O4-S

MOLECULAR WEIGHT :: 369.53

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1024 mg/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4401822

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 175 mg/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4401822

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 224 mg/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4401822

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 56 mg/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4401822

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Precautionary Statements ]:
P301 + P312 + P330

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xn:Harmful

[ Risk Phrases ]:
R22

[ Safety Phrases ]:
S22-S24/25

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
CV2308701

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

The antipsychotic amisulpride: ultrastructural evidence of its secretory activity in salivary glands.

Oral Dis. 20(8) , 796-802, (2014)

Amisulpride is reported to inhibit clozapine-induced sialorrhea. Preclinically, clozapine evokes muscarinic-M1-type-mediated secretion that, however, amisulpride does not reduce. Instead, amisulpride,...

A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia.

Int. Clin. Psychopharmacol. 19 , 63-69, (2004)

Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, doub...