(S)-Amisulpride
(Synonyms: (S)-氨磺必利; Esamisulpride; SEP-4199) 目录号 : GC63655
(S)-Amisulpride (Esamisulpride) 是一种有效的多巴胺 D2/D3 受体拮抗剂。(S)-Amisulpride 是 5-HT7 受体的拮抗剂，KI 值为 900 nM。(S)-Amisulpride 具有抗精神和抗抑郁作用。
Cas No.:71675-92-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
(S)-Amisulpride (Esamisulpride) is a potent dopamine D2/D3 receptor antagonist. (S)-Amisulpride is an antagonist at the 5-HT7 receptor with a KI of 900 nM. (S)-Amisulpride has antipsychotic and antidepressant effects[1][2].
(S)-Amisulpride (Esamisulpride) displays high affinity binding at both D2 and D3 receptors and is approximately twice as potent as racamisulpride and 20-50 times more potent than (R)-amisulpride at these receptors[2]
The (S)-amisulpride (10mg/kg, s.c.) stimulus is rapidly acquired and was shown to be dose-related, time dependent (effective between 30 and 120min) and stereoselective male C57BL/6 mice[1].
[1]. Timothy J Donahue, et al. (S)-amisulpride as a discriminative stimulus in C57BL/6 mice and its comparison to the stimulus effects of typical and atypical antipsychotics. Eur J Pharmacol. 2014 Jul 5;734:15-22.
[2]. Vincent Grattan, et al. Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D2 and D3, while R Enantiomers Engage 5-HT7. ACS Omega. 2019 Aug 15;4(9):14151-14154.
| Cas No. | 71675-92-8 | SDF | |
| 别名 | (S)-氨磺必利; Esamisulpride; SEP-4199 | ||
| 分子式 | C17H27N3O4S | 分子量 | 369.48 |
| 溶解度 | DMSO : 100 mg/mL (270.65 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7065 mL | 13.5325 mL | 27.0651 mL |
| 5 mM | 0.5413 mL | 2.7065 mL | 5.413 mL |
| 10 mM | 0.2707 mL | 1.3533 mL | 2.7065 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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2.
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(S)-Amisulpride as a discriminative stimulus in C57BL/6 mice and its comparison to the stimulus effects of typical and atypical antipsychotics
Eur J Pharmacol 2014 Jul 5;734:15-22.PMID:24726559DOI:10.1016/j.ejphar.2014.03.047.
Amisulpride, a substituted benzamide derivative, exerts atypical antipsychotic and antidepressant clinical effects and its (S)-stereoisomer is thought to underlie these actions. In the present study, male C57BL/6 mice were trained to discriminate (S)-Amisulpride (10mg/kg, s.c.) from vehicle in a two-lever drug discrimination task for food reward. The (S)-Amisulpride stimulus was rapidly acquired and was shown to be dose-related, time dependent (effective between 30 and 120min) and stereoselective: (S)-Amisulpride (ED50=1.77mg/kg; 4.2µmol/kg) was about three times more potent than rac-amisulpride (ED50=4.94mg/kg; 13.4µmol/kg) and ten times more potent than (R)-amisulpride (ED50=15.84mg/kg; 42.9µmol/kg). In tests of stimulus generalization, the (S)-Amisulpride stimulus generalized completely to sulpiride (ED50=12.67mg/kg; 37.1µmol/kg), a benzamide analog that also is purported to be an atypical antipsychotic, but did not fully generalize to the typical antipsychotic drug haloperidol (maximum of 45% drug-lever responding) nor to the atypical antipsychotic drugs clozapine (partial substitution of 65% drug-lever responding) or aripiprazole (~30% drug-lever responding). These results demonstrated that (S)-Amisulpride appears to exert a unique discriminative stimulus effect that is similar to other benzamides, but which differs from other structural classes of antipsychotic drugs.
(-)S amisulpride binds with high affinity to cloned dopamine D(3) and D(2) receptors
Eur J Pharmacol 2001 Dec 7;432(2-3):143-7.PMID:11740949DOI:10.1016/s0014-2999(01)01484-4.
Amisulpride is a substituted benzamide antipsychotic with nanomolar affinity and high selectivity for dopamine D(2) and dopamine D(3) receptors. The interaction of racemic (+/-)RS amisulpride and its two enantiomers (+)R and (-)S with dopamine D(2) and dopamine D(3) receptors subtypes were compared with that of haloperidol. Binding studies were performed using either [3H]spiperone or [3H]nemonapride in baculovirus/Spodoptera frugiperda insect (Sf-9) cell system expressing either the human dopamine recombinant D(2)long (hD(2L)) or the rat dopamine recombinant D(3) (rD(3)) receptors. K(i) values at dopamine rD(3) receptors were similar regardless of the radioligand used, whereas at hD(2L) receptors values were higher using [3H]spiperone than [3H]nemonapride. However, the rank order of compound potency against radiolabeled spiperone or nemonapride both at dopamine hD(2L) and at dopamine rD(3) receptors was similar. (-)S amisulpride displaced [3H]spiperone or [3H]nemonapride binding from both dopamine hD(2L) or dopamine rD(3) receptors, being twofold more potent than the racemic form and 38-19-fold more potent than (+)R enantiomer. Both racemic and the (-)S enantiomer exhibited 2-4 ([3H]spiperone)- and 3-4 ([3H]nemonapride)-fold higher affinity than haloperidol for dopamine rD(3) receptor, respectively. The (+)R enantiomer has weaker affinity with respect to haloperidol for both dopamine hD(2L) and dopamine rD(3) receptors. Our results show that (-)S amisulpride is the active enantiomer of amisulpride, showing high affinity for dopamine D(3) and dopamine D(2) receptors.
Effect of the amisulpride isomers on rat catalepsy
Eur J Pharmacol 2002 May 24;444(1-2):69-74.PMID:12191584DOI:10.1016/s0014-2999(02)01602-3.
The substituted benzamide amisulpride is currently administered in its racemic form. In the present study, the biochemical and cataleptogenic profiles of the two enantiomers (R+ and S-) were compared with those of the racemic mixture. Displacement binding studies showed that the (S-)-isomer possesses an higher affinity for dopamine D2-like receptor (K(i) 5.2+/-0.4 nM) compared to (R+)-Amisulpride (K(i) 244+/-12 nM) and to (RS)-Amisulpride (K(i) 9.8+/-0.8 nM). In contrast, (S-)-Amisulpride binds the alpha(2)-receptor with an affinity (K(i) 1528+/-45 nM) lower than that of the (R+)-isomer (K(i) 375+/-34 nM) and of (RS)-Amisulpride (K(i) 783+/-27 nM). The bar test was used to evaluate the catalepsy induced by each drug. (RS)-Amisulpride induced catalepsy only at very high doses (>100 mg/kg, S.c.) whereas, (S-)-Amisulpride produced a catalepsy at a lower dose (30 mg/kg, S.c.) and (R+)-Amisulpride did not produce any catalepsy up to the dose of 75 mg/kg. Interestingly, (R+)-Amisulpride reduced the catalepsy induced by (S-)-Amisulpride (50 mg/kg, S.c.) or haloperidol (0.3 mg/kg, S.c.), at the doses of 50 or 30 mg/kg, respectively. These results indicate that the weak cataleptic properties of (RS)-Amisulpride might partially rely on its (R+)-isomer and provide a further explanation for the atypical properties of amisulpride as an antipsychotic.
Effect of the amisulpride isomers on rat prolactinemia
Eur J Pharmacol 2002 Jul 19;448(2-3):263-6.PMID:12144950DOI:10.1016/s0014-2999(02)01990-8.
The effects on rat serum prolactin level of the two isomers constituting the racemic form of amisulpride were compared. (S-)-Amisulpride induced hyperprolactinemia at lower doses (ED(50) = 0.09 +/- 0.01 mg/kg) than racemic- (ED(50) = 0.24 +/- 0.03 mg/kg) and (R+)-Amisulpride (ED(50) = 4.13 +/- 0.05 mg/kg), in accord with their affinities for pituitary dopamine D(2) receptor (K(i) = 3.8 +/- 0.2, 6.4 +/- 0.2 and 143.3 +/- 2.3 nM, respectively). At doses twice the ED(50), (S-)-Amisulpride produced a maximal increase in prolactin level similar to that of the racemic form (403 +/- 21% and 425 +/- 15%, respectively), but higher than that of (R+)-Amisulpride (198 +/- 8%). These results suggest that the hyperprolactinemia induced by the racemic-amisulpride is mostly due to its (S-)-isomer.
Discriminative stimulus properties of the atypical antipsychotic amisulpride: comparison to its isomers and to other benzamide derivatives, antipsychotic, antidepressant, and antianxiety drugs in C57BL/6 mice
Psychopharmacology (Berl) 2017 Dec;234(23-24):3507-3520.PMID:28921163DOI:10.1007/s00213-017-4738-y.
Rationale: Racemic (RS)-amisulpride (Solian®) is an atypical antipsychotic drug used to treat schizophrenia and dysthymia. Blockade of dopamine D2/D3 and/or serotonin 5-HT7 receptors is implicated in its pharmacological effects. While the (S)-Amisulpride isomer possesses a robust discriminative cue, discriminative stimulus properties of (RS)-amisulpride have not been evaluated. Objectives: The present study established (RS)-amisulpride as a discriminative stimulus and assessed amisulpride-like effects of amisulpride stereoisomers, other benzamide derivatives, and antipsychotic, antidepressant, and anxiolytic drugs. Methods: Adult, male C57BL/6 mice were trained to discriminate 10 mg/kg (RS)-amisulpride from vehicle in a two-lever food-reinforced operant conditioning task. Results: (RS)-Amisulpride's discriminative stimulus was dose-related, time-dependent, and stereoselective. (S)-Amisulpride (an effective dose of 50% (ED50) = 0.21 mg/kg) was three times more potent than (RS)-amisulpride (ED50 = 0.60 mg/kg) or (R)-amisulpride (ED50 = 0.68 mg/kg). (RS)-Amisulpride generalized fully to the structurally related atypical antipsychotic/antidysthymia drug sulpiride (Sulpor®; ED50 = 7.29 mg/kg) and its (S)-enantiomer (ED50 = 9.12 mg/kg); moderate to high partial generalization [60-75% drug lever responding (%DLR)] occurred to the benzamide analogs tiapride (Tiapridal®) and raclopride, but less than 60% DLR to metoclopramide (Reglan®), nemonapride (Emilace®), and zacopride. Antipsychotic, antidepressant, and antianxiety drugs from other chemical classes (chlorpromazine, quetiapine, risperidone, and mianserin) produced 35-55% amisulpride lever responding. Lastly, less than 35% DLR occurred for clozapine, olanzapine, aripiprazole imipramine, chlordiazepoxide, and bupropion. Conclusions: (RS)-Amisulpride generalized to some, but not all benzamide derivatives, and it failed to generalize to any other antipsychotic, antidepressant, or antianxiety drugs tested. Interestingly, the (R)-isomer shared very strong stimulus properties with (RS)-amisulpride. This finding was in contrast to findings from Donahue et al. (Eur J Pharmacol 734:15-22, 2014), which found that the (R)-isomer did not share very strong stimulus properties when the (S)-isomer was the training drug.