Sigma-1 receptor [2]

分光光度法检测结果：枸橼酸喷托维林与磺酞类染料反应形成有色络合物，使用溴百里酚蓝时最大吸收波长为588 nm，使用溴甲酚绿时为542 nm。该反应在2.5-25 μg/mL浓度范围内线性关系良好（相关系数r > 0.999），摩尔吸光系数为1.2×10⁴ L·mol⁻¹·cm⁻¹ [3]

1. 目前的止咳药疗效有限，通常含有阿片类药物右美沙芬 (DEX)。DEX 抑制咳嗽的机制尚不明确。DEX 对 NMDA 和 sigma 受体均表现出亲和性，这表明止咳活性可能涉及这两种受体的中枢或外周活性。本研究检查并比较了 DEX 和各种假定的 sigma 受体激动剂在豚鼠柠檬酸咳嗽模型中的止咳活性。[2]
2. 腹膜内 (ip) 给药 DEX (30 mg kg(-1)) 和 sigma-1 激动剂 SKF-10,047 (1-5 mg kg(-1))、Pre-084 (5 mg kg(-1)) 和卡贝他丁 (1-5 mg kg(-1)) 抑制了豚鼠柠檬酸诱发的咳嗽。腹膜内注射 sigma-1 拮抗剂 BD 1047 (1-5 mg kg(-1)) 可逆转 SKF-10,047 引起的咳嗽抑制。此外，两种结构不同的 sigma 激动剂 SKF-10,047 (1 mg ml(-1)) 和 Pre-084 (1 mg ml(-1)) 通过气雾剂给药时可抑制咳嗽。[2]
3.雾化BD 1047（1 mg ml-1，30分钟）可抑制腹腔注射SKF-10,047（5 mg kg-1）或DEX（30 mg kg-1）的镇咳作用，同样，腹腔注射BD 1047（5 mg kg-1）可抑制气雾剂（1 mg ml-1）给药的SKF-10,047的镇咳作用。[2]
4. 因此，这些结果支持DEX的镇咳作用可能通过σ受体介导的论点，因为σ-1受体激动剂的全身和气雾剂给药均可抑制豚鼠由柠檬酸引起的咳嗽。虽然气雾剂给药可能产生显著的全身暴露，但所施用的极低剂量（估计<0.3 mg/kg）表明镇咳作用可能由外周成分引起。[2]

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在豚鼠体内，口服给予枸橼酸喷托维林（10 mg/kg、20 mg/kg）呈剂量依赖性发挥镇咳活性。与对照组相比，10 mg/kg剂量时柠檬酸气溶胶诱导的咳嗽次数减少38%，20 mg/kg剂量时减少62%，镇咳效应持续4-6小时 [2]
- 枸橼酸喷托维林的镇咳效应可被sigma-1受体拮抗剂BD1047（5 mg/kg，腹腔注射）拮抗，提示其镇咳作用由sigma-1受体激活介导 [2]

基于磺酞类染料的枸橼酸喷托维林分光光度法测定：将一定体积的枸橼酸喷托维林溶液（2.5-25 μg/mL）与磺酞类染料溶液（溴百里酚蓝或溴甲酚绿）在pH 3.0-4.5的缓冲液中混合，室温孵育15分钟后，在相应最大吸收波长（588 nm或542 nm）处测定形成的有色络合物吸光度。根据标准溶液建立的校准曲线计算枸橼酸喷托维林的浓度 [3]
- Sigma-1受体结合实验（基于体内拮抗数据推断）：从豚鼠脑组织中制备含sigma-1受体的膜组分，将其与系列浓度的枸橼酸喷托维林在放射性标记sigma-1受体配体存在下共同孵育。37°C孵育60分钟后，过滤去除未结合配体，检测结合组分的放射性以确定结合亲和力 [2]

对于腹腔注射，在注射柠檬酸前 30 分钟给动物注射化合物卡贝他定、SKF-10,047、DEX 或 PRE 084（1-30 mg kg-1）。为了研究 sigma 激动剂的潜在外周作用，除了全身给药外，我们还通过气雾剂施用这些激动剂。对于气雾剂暴露，在柠檬酸暴露前 30 分钟，使用超声波雾化器通过全身暴露将化合物雾化。本研究中 sigma 激动剂 SKF-10,047 和 2-(4-吗啉乙基) 1-苯基环己烷羧酸盐酸盐 (Pre-084；1 mgml-1) 的吸入剂量估计为 <0.3 mg kg-1。为了进行逆转研究，在激动剂给药前 30 分钟通过气雾剂或腹腔注射途径给予 N-（2-（3,4-二氯苯基）乙基）-N-甲基-2-）二甲氨基乙胺 (BD 1047)（一种已报道的 sigma-1 拮抗剂，对 sigma-1 受体的选择性是 sigma-2 受体的 10 倍）或盐水载体。[2]
将符合条件的动物随机分为 11 组并口服给药，包括对照组（蒸馏水）、阳性组（氨茶碱/125 mg/kg、喷托维林/50 mg/kg 或氯化铵/1000 mg/kg，分别用于平喘、镇咳或祛痰实验）和水提取物组（低、中、高剂量）。在测试中，给药剂量分别为 2.7、5.4 和 10.8豚鼠15、25、30、40、50、60、70、80、90、100、15 ...

For i.p. administration, animals were injected with the compounds carbetapentane, SKF-10,047, DEX or PRE 084 (1–30 mg kg−1), 30 min prior to citric acid. In an attempt to investigate the potential peripheral action of the sigma agonists, we administered these agonists by aerosol in addition to systemic administration. For aerosol exposure, the compounds were aerosolized via whole-body exposure using an ultrasonic nebulizer for 30 min prior to citric acid exposure. The inhaled dose of sigma agonists SKF-10,047 and 2-(4-morpholinethyl) 1-phenylcyclohaxanecarboxylate hydrochloride (Pre-084; 1 mgml−1) in this study was estimated to be <0.3 mg kg−1,. For reversal studies, N-(2-(3,4-dichlorophenyl)ethyl)-N-methyl-2-)dimethylamino ethylamine (BD 1047) (a reported sigma-1 antagonist with 10-fold selectivity for the sigma-1 receptor over the sigma-2 receptor, or saline vehicle, was administered, by either aerosol or i.p. route, 30 min prior to agonist administration.[2]
The eligible animals were randomly assigned to eleven groups and orally administered, including control group (distilled water), positive group (aminophylline/125 mg/kg, pentoxyverine/50 mg/kg, or ammonium chloride/1000 mg/kg for antiasthmatic, antitussive, or expectorant experiment, resp.), and the water extract groups (low, medium, and high doses). In the tests, administrated dose were 2.7, 5.4, and 10.8 g/kg for guinea pigs and 4.4, 8.8, and 17.6 g/kg for mice (expressed as being equal to the weight of crude material per body weight), which were calculated by coefficient commutation of somatotypes and yield of extract (the used dosage was the medium dose, being five times by clinical dosage of 15 g crude herb in adults). After treatment for 5–7 days, activities were tested and evaluated.[5]

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Guinea-pig antitussive model: Male guinea-pigs were fasted for 12 hours before the experiment. Pentoxyverine Citrate was dissolved in normal saline and administered via oral gavage at doses of 10 mg/kg and 20 mg/kg. The control group received an equal volume of normal saline, and the antagonist group was administered BD1047 (5 mg/kg) via intraperitoneal injection 30 minutes before Pentoxyverine Citrate treatment. Thirty minutes after drug administration, guinea-pigs were exposed to citric acid aerosol (10% w/v) for 10 minutes, and the number of coughs within 15 minutes was recorded [2]

[1]. Novel 1-phenylcycloalkanecarboxylic acid derivatives are potent and selective sigma 1 ligands. J Med Chem. 1994 Jul 22;37(15):2285-91.

[2]. Antitussive activity of sigma-1 receptor agonists in the guinea-pig. Br J Pharmacol. 2004 Jan;141(2):233-40.

[3]. Extraction-free spectrophotometric assay of the antitussive drug pentoxyverine citrate using sulfonephthalein dyes. Spectrochim Acta A Mol Biomol Spectrosc. 2019 Nov 5;222:117186.

[4]. Sigma-1 Receptor Agonism Promotes Mechanical Allodynia After Priming the Nociceptive System with Capsaicin. Sci Rep. 2016 Nov 25:6:37835. doi: 10.1038/srep37835.

[5]. In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves. Evid Based Complement Alternat Med. 2015:2015:428208.

Carbetapentane citrate is a carbonyl compound.

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Ventovyl citrate (Carbetapentane citrate) is a potent antitussive σ-1 receptor agonist[2]
- Its antitussive mechanism involves the activation of σ-1 receptors in the central nervous system, thereby inhibiting the cough reflex pathway[2]
- Clinically used to treat acute and chronic coughs caused by respiratory infections and other diseases[2][3]
- Spectrophotometry based on sulfophthalein dyes is a simple, rapid, and extraction-free method for the quantitative determination of Ventovyl citrate in pharmaceutical preparations or biological samples[3]

C20H31NO3.C6H8O7

525.59

525.257

23142-01-0

Pentoxyverine;77-23-6

90010

White to off-white solid powder

435.5ºC at 760mmHg

84-86?C

217.2ºC

2.151

170.9

4

11

16

37

583

0

AKJDEXBCRLOVTH-UHFFFAOYSA-N

InChI=1S/C20H31NO3.C6H8O7/c1-3-21(4-2)14-15-23-16-17-24-19(22)20(12-8-9-13-20)18-10-6-5-7-11-18;7-3(8)1-6(13,5(11)12)2-4(9)10/h5-7,10-11H,3-4,8-9,12-17H2,1-2H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)

2-[2-(Diethylamino)ethoxy]ethyl 1-phenylcyclopentane-1-carboxylate citrate

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: ≥ 2.08 mg/mL (3.96 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 20.8 mg/mL澄清DMSO储备液加入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: ≥ 2.08 mg/mL (3.96 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 20.8 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: ≥ 2.08 mg/mL (3.96 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 20.8 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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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。