H1 Receptor

Cyclizine hydrochloride (100 μM) greatly reduces the levels of iNOS protein and nitrite buildup in the supernatants of LPS-stimulated RAW 264.7 cells[1]. With an IC50 of 5.42 µM, cyclidine hydrochloride suppresses the release of histamine from isolated human lung segments produced by anti-IgE [2].

Mice's locomotor activity is enhanced by cyclizine hydrochloride (1–10 mg/kg) in a dose-dependent manner[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

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

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)