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
BENZHYDROLPIPERAZINES & THEIR N-DEALKYLATION PRODUCTS ARE DISTRIBUTED IN ALL TISSUES OF RAT & ARE TRANSFERRED TO FETUS. /BENZYHYDROLPIPERAZINES/

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Metabolism / Metabolites
Cyclizine is metabolised to its N-demethylated derivative, norcyclizine, which has little antihistaminic (H1) activity compared to Cyclizine.
OXIDATIVE N-DEALKYLATION IS MAIN METABOLIC PATHWAY OF BENZHYDROLPIPERAZINES; CYCLIZINE.../IS/ TRANSFORMED INTO NORCYCLIZINE...
WITH A PURIFIED MIXED FUNCTION OXIDASE FROM LIVER MICROSOMES IN PRESENCE OF REDUCED PYRIDINE NUCLEOTIDE & O2.../CYCLIZINE IS/ OXIDIZED TO N-OXIDE.

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Biological Half-Life
20 hours

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Occasional doses of cyclizine are probably acceptable during breastfeeding. Large doses or more prolonged use may cause effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established.
◉ Effects in Breastfed Infants
Relevant published information on cyclizine was not found as of the revision date. In one telephone follow-up study, mothers reported irritability and colicky symptoms 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention and none of the infants were exposed to cyclizine.
◉ Effects on Lactation and Breastmilk
Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of antihistamines have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Interactions
COMBINATIONS OF CAFFEINE 100 MG WITH CYCLIZINE-HCL 50 & 100 MG DID NOT PRODUCE ANY SUBJECTIVE CHANGES OR CHANGES IN PERFORMANCE TESTS, DIFFERING FROM CONTROL.

[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 in which one nitrogen of the piperazine ring is substituted by a methyl group, while the other is substituted by a diphenylmethyl group. It has a role as an antiemetic, a cholinergic antagonist, a central nervous system depressant, a local anaesthetic and a H1-receptor antagonist.
A histamine H1 antagonist given by mouth or parenterally for the control of postoperative and drug-induced vomiting and in motion sickness. (From Martindale, The Extra Pharmacopoeia, 30th ed, p935)
A histamine H1 antagonist given by mouth or parenterally for the control of postoperative and drug-induced vomiting and in motion sickness. (From Martindale, The Extra Pharmacopoeia, 30th ed, p935)

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Drug Indication
For prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness, and vertigo (dizziness caused by other medical problems).

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Mechanism of Action
Vomiting (emesis) is essentially a protective mechanism for removing irritant or otherwise harmful substances from the upper GI tract. Emesis or vomiting is controlled by the vomiting centre in the medulla region of the brain, an important part of which is the chemotrigger zone (CTZ). The vomiting centre possesses neurons which are rich in muscarinic cholinergic and histamine containing synapses. These types of neurons are especially involved in transmission from the vestibular apparatus to the vomiting centre. Motion sickness principally involves overstimulation of these pathways due to various sensory stimuli. Hence the action of cyclizine which acts to block the histamine receptors in the vomiting centre and thus reduce activity along these pathways. Furthermore since cyclizine possesses anti-cholinergic properties as well, the muscarinic receptors are similarly blocked.
.../IT SEEMS/ THAT STIMULATION OF VESTIBULAR APPARATUS IS NECESSARY & SUFFICIENT...& THAT VESTIBULAR CEREBELLAR MIDBRAIN "INTEGRATIVE VOMITING CENTER" & MEDULLARY CHEMORECEPTIVE TRIGGER ZONE ARE...INVOLVED /IN MOTION SICKNESS/. IT IS...PROBABLE THAT EFFECTIVE ANTIHISTAMINES EXERT.../ACTION/ IN THESE CENTERS. /ANTIHISTAMINE/

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Therapeutic Uses
Antiemetics; Histamine H1 Antagonists
ANTIHISTAMINE USED AS HYDROCHLORIDE & LACTATE IN PREVENTION & TREATMENT OF MOTION SICKNESS (NAUSEA, VOMITING & VERTIGO). IT IS ALSO PROBABLY EFFECTIVE FOR CONTROL OF POSTOPERATIVE NAUSEA & VOMITING.
DURATION OF ACTION IS ABOUT 4 HR.
...LARGE SCALE STUDY, INCL PREGNANT WOMEN RECEIVING CYCLIZINE DURING 1ST TRIMESTER, FAILED TO CONFIRM THAT DRUG HAD ANY TERATOGENIC EFFECT IN MAN WITH DOSES EMPLOYED.
For more Therapeutic Uses (Complete) data for CYCLIZINE (7 total), please visit the HSDB record page.

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Drug Warnings
.../DO NOT/ EXCEED 4 TABLETS/DAY. /HYDROCHLORIDE/
.../IT/ SHOULD NOT BE USED IN WOMEN DURING PREGNANCY & THOSE LIKELY TO BECOME PREGNANT UNLESS SPECIFICALLY DIRECTED BY PHYSICIAN.
IN 1965 AN AD HOC COMMITTEE OF US FDA CONCLUDED THAT EVIDENCE OF TERATOGENIC EFFECTS IN HUMAN...WAS NOT SIGNIFICANT, BUT IT MADE NO SPECIFIC MENTION OF EYES.
...OFFSPRING OF PROBABLY SEVERAL THOUSAND WOMEN WHO HAD RECEIVED APPROX 150 MG CYCLIZINE/DAY DURING PREGNANCY...HAD A VARIETY OF NONOCULAR ABNORMALITIES, BUT STATISTICAL SIGNIFICANCE IN RELATION TO CYCLIZINE WAS UNCERTAIN.
For more Drug Warnings (Complete) data for CYCLIZINE (8 total), please visit the HSDB record page.

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Pharmacodynamics
Cyclizine is a piperazine-derivative antihistamine used as an antivertigo/antiemetic agent. Cyclizine is used in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Although the mechanism by which cyclizine exerts its antiemetic and antivertigo effects has not been fully elucidated, its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone. It also possesses anticholinergic, antihistaminic, 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。