H1 Receptor

Cyclizine 盐酸盐 (100 μM) 大大降低了 LPS 刺激的 RAW 264.7 细胞上清液中 iNOS 蛋白和亚硝酸盐积累的水平[1]。盐酸环己哌啶的 IC50 为 5.42 µM，可抑制抗 IgE 产生的离体人肺段释放组胺 [2]。

盐酸赛克利嗪（1-10 mg/kg）以剂量依赖性方式增强小鼠的运动活性[3]。

Absorption, Distribution and Excretion
Benzohydroxypiperazine and its N-dealkylation products are distributed in all tissues of rats and can be transferred to the fetus. /Benzohydroxypiperazine/

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Metabolism/Metabolites Cyclizine is metabolized to the N-demethylated derivative norCyclizine, which has weaker antihistamine (H1) activity compared to Cyclizine. Oxidative N-dealkylation is the major metabolic pathway of benzohydroxypiperazine; Cyclizine is converted to norCyclizine by a mixed-function oxidase purified from liver microsomes in the presence of reduced pyridine nucleotides and oxygen. Cyclizine is oxidized to N-oxide. Biological half-life: 20 hours

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Occasional use of cyclorhizine during lactation may be acceptable. High doses or prolonged use may affect the infant or reduce milk production, especially when used in combination with sympathomimetic drugs (such as pseudoephedrine) or before lactation is fully established.
◉ Effects on Breastfed Infants
As of the revision date, no published information was found regarding cyclorhizine. In a telephone follow-up study, mothers reported irritability and colic in 10% of their infants after taking various antihistamines, and lethargy in 1.6%. All adverse reactions did not require medical intervention, and all infants were previously unexposed to cyclorhizine.
◉ Effects on Lactation and Breast Milk
Higher doses of injected antihistamines can lower baseline serum prolactin levels in non-lactating women and early postpartum women. However, pre-administration of antihistamines by postpartum mothers does not affect lactation-induced prolactin secretion. Whether lower doses of oral antihistamines have the same effect on serum prolactin levels, and whether their effect on prolactin has any impact on breastfeeding success, is currently unknown. For established lactating mothers, prolactin levels may not affect their ability to breastfeed.

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Interactions
The combination of 100 mg caffeine with 50 mg and 100 mg cyclorhizine hydrochloride did not produce any subjective changes or performance test changes, unlike the control group.

[1]. The effects of H1-antihistamines on the nitric oxide production by RAW 264.7 cells with respect to their lipophilicity. Int Immunopharmacol. 2009 Jul;9(7-8):990-5.

[2]. Inhibition of histamine release from human lung in vitro by antihistamines and related drugs. Br J Pharmacol. 1980 Aug;69(4):663-7.

[3]. Effects of antihistaminics on locomotor activity in mice. Comparison with opiate and amphetamine-induced hyperactivity. Gen Pharmacol. 1991;22(2):293-6.

Cyclizine is an N-alkylpiperazine compound in which one nitrogen atom of the piperazine ring is replaced by a methyl group and the other nitrogen atom is replaced by a diphenylmethyl group. It has antiemetic, cholinergic, central nervous system depressant, local anesthetic, and H1 receptor antagonist effects. It is a histamine H1 receptor antagonist, which can be administered orally or parenterally for the control of postoperative vomiting, drug-induced vomiting, and motion sickness. (Excerpt from Martindale Pharmacopoeia, 30th edition, p. 935) Indications: Used for the prevention and treatment of nausea, vomiting, and dizziness caused by motion sickness, as well as dizziness caused by other diseases. Mechanism of Action: Vomiting is essentially a protective mechanism used to clear irritants or other harmful substances from the upper digestive tract. Vomiting is controlled by the vomiting center in the medulla oblongata of the brain, of which the chemoreceptor trigger zone (CTZ) is a key component. The vomiting center contains synapses rich in muscarinic cholinergic and histaminergic neurons. These types of neurons are particularly involved in signal transmission from the vestibular system to the vomiting center. Motion sickness primarily involves various sensory stimuli leading to overexcitation of these pathways. Therefore, the mechanism of action of cyclorhizine is to block histamine receptors in the vomiting center, thereby reducing the activity of these pathways. Furthermore, because cyclorhizine also has anticholinergic properties, muscarinic receptors are also blocked. …It seems that stimulation of the vestibular system is necessary and sufficient…and the vestibular-cerebellar-midbrain “integrated vomiting center” and the medullary chemoreceptor trigger zone…are involved in/motion sickness/. Effective antihistamines are likely to act in these centers. /Antihistamines/

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Therapeutic Uses
Antiemetic; Histamine H1 receptor antagonist
Antihistamines hydrochloride and lactate are used for the prevention and treatment of motion sickness (nausea, vomiting, and dizziness). It may also be effective in controlling postoperative nausea and vomiting.
The duration of action is approximately 4 hours.
…A large-scale study, including pregnant women taking cyclorhizine in early pregnancy, failed to confirm any teratogenic effects of this drug in humans at the doses used.
For more complete data on the therapeutic uses of cyclorhizine (7 types), please visit the HSDB record page.

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Drug Warnings
…/Do not/take more than 4 tablets daily. Hydrochloride
…This product should not be used by pregnant women or women who may become pregnant unless specifically directed by a physician.
In 1965, a special committee of the U.S. Food and Drug Administration (FDA) concluded that the evidence of teratogenic effects of this product in humans was not significant, but did not specifically mention the eyes.
...The offspring of thousands of women who took approximately 150 mg of cyclorhizine hydrochloride daily during pregnancy...experienced a variety of non-ocular abnormalities, but none were statistically significant in relation to cyclorhizine hydrochloride. Uncertain.
For more complete data on drug warnings (of 8) for cyclorhizine, please visit the HSDB records page.

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Pharmacodynamics
Cyclorhizine is a piperazine derivative antihistamine used as an anti-vertigo/antiemetic. Cyclorhizine is used to prevent and treat nausea, vomiting, and dizziness associated with motion sickness. It is also used to treat vertigo caused by disorders affecting the vestibular system. Although the mechanism by which cyclorhizine exerts its antiemetic and anti-vertigo effects is not fully elucidated, its central anticholinergic properties are partly responsible. The drug inhibits labyrinthine excitability and vestibular stimulation and may affect the medullary chemoreceptor trigger zone. It also has anticholinergic, antihistamine, central nervous system depressant, and local anesthetic effects.

C18H23CLN2

302.84

302.155

303-25-3

Cyclizine;82-92-8;Cyclizine dihydrochloride;5897-18-7;Cyclizine lactate;5897-19-8

6726

CRYSTALS FROM PETROLEUM ETHER
WHITE OR CREAMY WHITE CRYSTALLINE POWDER

363.7ºC at 760mmHg

258-260ºC

159.1ºC

3.701

6.48

0

2

3

20

253

0

Cl.CN1CCN(C(C2C=CC=CC=2)C2C=CC=CC=2)CC1

UVKZSORBKUEBAZ-UHFFFAOYSA-N

InChI=1S/C18H22N2/c1-19-12-14-20(15-13-19)18(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18H,12-15H2,1H3

1-benzhydryl-4-methylpiperazine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。