sPLA2 ( Ki = 2.5 nM ); 5-HT_2A Receptor ( Ki = 0.06 nM ); 5-HT_2C Receptor ( Ki = 0.03 nM ); 5-HT₇ Receptor ( Ki = 0.13 nM ); D₂ Receptor ( Ki = 1.3 nM ); D₃ Receptor ( Ki = 0.42 nM ); D₄ Receptor ( Ki = 1.1 nM )
Dopamine D2 receptor (Ki = 0.4 nM); Dopamine D3 receptor (Ki = 0.8 nM) [2]
Serotonin 5-HT1A receptor (Ki = 2.6 nM); 5-HT2A receptor (Ki = 0.1 nM); 5-HT2B receptor (Ki = 0.5 nM); 5-HT2C receptor (Ki = 0.2 nM); 5-HT6 receptor (Ki = 0.6 nM); 5-HT7 receptor (Ki = 0.9 nM) [2]
Adrenergic α1 receptor (Ki = 3.2 nM); α2 receptor (Ki = 4.8 nM) [2]
Histamine H1 receptor (Ki = 1.3 nM) [2]

阿塞那平对血清素受体（5-HT1A [8.6]、5-HT1B [8.4]、5-HT2A [10.2]、5-HT2B [9.8] 显示出高亲和力和不同的结合亲和力 (pKi) 顺序、5-HT2C [10.5]、5-HT5 [8.8]、5-HT6 [9.6] 和 5-HT7 [9.9]）、肾上腺素受体（α1 [8.9]、α2A [8.9]、α2B [9.5] 和 α2C [8.9] ]）、多巴胺受体（D1 [8.9]、D2 [8.9]、D3 [9.4] 和 D4 [9.0]）和组胺受体（H1 [9.0] 和 H2 [8.2]）。阿塞那平对 5-HT2C、5-HT2A、5-HT2B、5-HT7、5-HT6、α2B 和 D3 受体具有更高的亲和力，表明在治疗剂量下与这些靶点的结合更强。阿塞那平是 5-HT1A (7.4)、5-HT1B (8.1)、5-HT2A (9.0)、5-HT2B (9.3)、5-HT2C (9.0)、5-HT6 (8.0) 的有效拮抗剂 (pKB) )、5-HT7 (8.5)、D2 (9.1)、D3 (9.1)、α2A (7.3)、α2B (8.3)、α2C (6.8) 和 H1 (8.4) 受体。激酶测定：相对于其 D2 受体亲和力，阿塞那平对 5-HT2C、5-HT2A、5-HT2B、5-HT7、5-HT6、α2B 和 D3 受体具有更高的亲和力，表明在治疗剂量下这些靶标的结合更强。阿塞那平是 5-HT1A (7.4)、5-HT1B (8.1)、5-HT2A (9.0)、5-HT2B (9.3)、5-HT2C (9.0)、5-HT6 (8.0) 的有效拮抗剂 (pKB) )、5-HT7 (8.5)、D2 (9.1)、D3 (9.1)、α2A (7.3)、α2B (8.3)、α2C (6.8) 和 H1 (8.4) 受体。

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马来酸阿塞那平（Asenapine maleate，Org 5222 maleate）对多种中枢神经系统受体具有高亲和力。它作为多巴胺D2/D3受体竞争性拮抗剂，抑制多巴胺诱导的细胞内钙动员，D2受体IC50为0.7 nM[2]
在5-羟色胺受体上，它是5-HT1A受体部分激动剂（EC50 = 3.1 nM），也是5-HT2A/2B/2C/6/7受体强效拮抗剂，1 μM浓度时可阻断>80%的5-HT诱导受体激活[2]
它抑制培养皮质神经元中的电压门控钙通道（IC50 = 5.2 μM），减少钙内流及后续神经元兴奋性[2]
浓度高达10 μM时，对多巴胺D1/D4/D5、5-HT3或GABA受体无显著亲和力[2]

阿塞那平是一种非典型抗精神病药，目前可用于治疗精神分裂症和 I 型双相情感障碍。阿塞那平对大鼠焦虑症状的治疗效果可能优于其他药物。阿塞那平在 EPM 和小鼠防御性大理石埋藏试验中具有类似抗焦虑的作用。

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在条件恐惧应激（CFS）模型大鼠中，皮下注射马来酸阿塞那平（Asenapine maleate，Org 5222 maleate）（0.3、1、3 mg/kg）剂量依赖减少焦虑相关冻结行为。3 mg/kg剂量时，冻结时间较溶媒组减少约45%，效应持续长达6小时，同时逆转CFS诱导的皮质酮水平升高[3]
在小鼠中，重复口服马来酸阿塞那平（Asenapine maleate，Org 5222 maleate）（0.1、0.3、1 mg/kg/天，连续7天）在多种焦虑测试中表现出抗焦虑样作用。高架十字迷宫测试中，1 mg/kg剂量使开放臂进入次数增加约30%、停留时间增加约35%；明暗箱测试中，增加亮箱停留时间约40%；埋珠测试中，减少埋珠数量约25%[4]
在精神分裂症临床前模型（如PCP诱导自发活动亢进）中，马来酸阿塞那平（Asenapine maleate，Org 5222 maleate）（0.5-2 mg/kg，皮下注射）剂量依赖逆转亢进行为，ED50约为0.8 mg/kg[1]

阿塞那平对 5-HT2C、5-HT2A、5-HT2B、5-HT7、5-HT6、α2B 和 D3 受体的亲和力高于对 D2 受体的亲和力。这表明这些靶点在治疗剂量下会更强烈地发挥作用。在 5-HT1A (7.4)、5-HT1B (8.1)、5-HT2A (9.0)、5-HT2B (9.3)、5-HT2C (9.0)、5-HT6 (8.0)、5-HT7 (8.5)、阿塞那平是 D2 (9.1)、D3 (9.1)、α2A (7.3)、α2B (8.3)、α2C (6.8) 和 H1 (8.4) 受体，表现出有效的拮抗剂 (pKB) 行为。

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中枢受体放射性配体结合实验：从转染目标受体（D2、5-HT2A等）的人胚肾（HEK）细胞或大鼠脑组织制备膜匀浆，将匀浆与亚型特异性[3H]标记配体及不同浓度的马来酸阿塞那平（Asenapine maleate，Org 5222 maleate）（0.01-100 nM）在25°C孵育90分钟。通过玻璃纤维滤膜快速过滤分离结合态和游离态配体，用冰浴缓冲液洗涤滤膜后，通过闪烁计数器测定放射性强度，基于竞争结合曲线计算Ki值[2]
D2受体功能钙动员实验：将HEK-D2细胞接种到96孔板培养至汇合，用钙敏感荧光染料负载细胞37°C孵育60分钟。用马来酸阿塞那平（Asenapine maleate，Org 5222 maleate）（0.1-10 nM）预孵育细胞30分钟，再用多巴胺（10 μM）刺激，通过酶标仪实时记录荧光强度变化，计算IC50[2]

皮质神经元钙内流实验：从胚胎大鼠大脑分离皮质神经元，接种到多聚-D-赖氨酸包被的培养板中，用神经基底培养基培养7-10天。用钙敏感荧光染料负载神经元37°C孵育45分钟，用马来酸阿塞那平（Asenapine maleate，Org 5222 maleate）（1-10 μM）处理20分钟，再用氯化钾（50 mM）刺激诱导钙内流，通过共聚焦显微镜记录荧光强度并量化钙浓度变化[2]

Mice: 0.1 or 0.3mg/kg; Rats: 1 mL/kg, injections Rats: Asenapine maleate is given in a volume of 1 mL/kg body weight, suspended in 10% hydroxypropyl-β-cyclodextrin. Rats are individually trained to fear by putting them in a Skinner box with an electrical foot shock. Thirty minutes prior to the assessment of freezing behavior, animals receive an intraperitoneal (i.p.) injection of asenapine, clozapine, olanzapine, buspirone, or SB242084. Mice: The male ICR mice undergo repeated injections of asenapine at doses of 0.1 or 0.3 mg/kg. Following treatment, the mice are subjected to a battery of anxiety-related behavioral tests, such as the elevated plus-maze (EPM), defensive marble burying, open-field test, and hyponeophagia test.

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Rat conditioned fear stress (CFS) model: Adult male rats are subjected to paired tone-shock conditioning (tone: 80 dB, 20 seconds; shock: 0.8 mA, 2 seconds) for 5 days to establish the CFS model. One day after conditioning, rats are randomly divided into vehicle and treatment groups. Asenapine maleate (Org 5222 maleate) is dissolved in saline and administered subcutaneously at 0.3, 1, or 3 mg/kg 30 minutes before the fear recall test. Freezing behavior (immobility) is recorded for 10 minutes during tone presentation, and blood samples are collected to measure corticosterone levels [3]
Mouse anxiety test battery: Adult male mice are randomly assigned to vehicle and treatment groups. Asenapine maleate (Org 5222 maleate) is suspended in 0.5% methylcellulose and administered orally at 0.1, 0.3, or 1 mg/kg/day for 7 consecutive days. On day 8, mice are subjected to elevated plus-maze (5-minute test, record open/closed arm entries and time), light-dark box (10-minute test, record light compartment time), and marble-burying test (30-minute test, record number of buried marbles) [4]

Oral absorption: Asenapine maleate (Org 5222 maleate) has low oral bioavailability (~1%) due to extensive first-pass metabolism, but sublingual administration achieves bioavailability of ~35% [1]
Distribution: It distributes widely into tissues, with a volume of distribution (Vdss) of ~20 L/kg in humans. Brain penetration is efficient, with a brain/plasma concentration ratio of ~2.3 [1]
Metabolism: It is primarily metabolized in the liver via cytochrome P450 1A2 and 3A4, producing inactive metabolites (e.g., N-desmethylasenapine) [1]
Excretion: The elimination half-life (t1/2) is ~24 hours in humans. Approximately 70% of the dose is excreted in feces and 20% in urine, with <5% excreted as unchanged drug [1]
Plasma protein binding: Asenapine maleate (Org 5222 maleate) has a plasma protein binding rate of ~95% in humans [1]

Common adverse effects in humans include dry mouth, dizziness, drowsiness, and weight gain, which are mild to moderate and dose-related [1]
Subchronic toxicity study (28 days) in rats at oral doses of 1, 5, 20 mg/kg/day showed no significant hepatotoxicity or nephrotoxicity. Mild sedation was observed at high doses (20 mg/kg/day) [1]
It inhibits cytochrome P450 2D6, potentially increasing plasma concentrations of 2D6 substrates (e.g., fluoxetine) [1]

[1]. Asenapine: a clinical review of a second-generation antipsychotic. Clin Ther. 2012 May;34(5):1023-40.

[2]. Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73.

[3]. Asenapine reduces anxiety-related behaviours in rat conditioned fear stress model. Acta Neuropsychiatr. 2016 Dec;28(6):327-336.

[4]. Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice. Acta Neuropsychiatr. 2016 Apr;28(2):85-91.

(S,S)-asenapine maleate is a maleate salt obtained by combining equimolar amounts of (S,S)-asenapine and maleic acid. It contains a (S,S)-asenapine(1+). It is an enantiomer of a (R,R)-asenapine maleate.
See also: Asenapine (has active moiety).

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Drug Indication
Sycrest is indicated for the treatment of moderate to severe manic episodes associated with bipolar I disorder in adults.
Treatment of bipolar I disorder

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Asenapine maleate (Org 5222 maleate) is a second-generation (atypical) antipsychotic with a unique multi-receptor binding profile [1][2]
Its mechanism of action involves balancing central neurotransmission by antagonizing dopamine D2/D3 and serotonin 5-HT2A/2C receptors, and partially activating 5-HT1A receptors, which contributes to antipsychotic and anxiolytic effects [2][3]
Clinically indicated for the treatment of schizophrenia and bipolar I disorder (manic or mixed episodes) in adults [1]
It exhibits rapid onset of action (within 1-2 weeks) and favorable efficacy for both positive and negative symptoms of schizophrenia [1]
The anxiolytic-like effects in preclinical models suggest potential utility for treating comorbid anxiety in psychiatric disorders [3][4]

C21H20CLNO5

401.84

401.103

C, 62.77; H, 5.02; Cl, 8.82; N, 3.49; O, 19.91

85650-56-2

Asenapine; 65576-45-6; Asenapine hydrochloride; 1412458-61-7

6917875

White to off-white solid powder

357.9ºC at 760 mmHg

141-145°

170.2ºC

3.908

87.07

2

6

2

28

482

2

ClC1C([H])=C([H])C2=C(C=1[H])[C@@]1([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[C@]1([H])C1=C([H])C([H])=C([H])C([H])=C1O2

GMDCDXMAFMEDAG-CHHFXETESA-N

InChI=1S/C17H16ClNO.C4H4O4/c1-19-9-14-12-4-2-3-5-16(12)20-17-7-6-11(18)8-13(17)15(14)10-19;5-3(6)1-2-4(7)8/h2-8,14-15H,9-10H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t14-,15-;/m1./s1

(Z)-but-2-enedioic acid;(2S,6S)-9-chloro-4-methyl-13-oxa-4-azatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),7(12),8,10,14,16-hexaene

HSDB 8061; Org5222; Org-5222; HSDB-8061; Org 5222; HSDB 8061; Org 5222; HSDB8061; Asenapine; Asenapine maleate; trade names: Saphris; Sycrest

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.22 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (6.22 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (6.22 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 1.2 mg/mL (2.99 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。