Metabolism / Metabolites
Cinnarizine has known human metabolites that include 4-{3-[4-(diphenylmethyl)piperazin-1-yl]prop-1-en-1-yl}phenol, Benzophenone, 1-Benzhydrylpiperazine, 4-{phenyl[4-(3-phenylprop-2-en-1-yl)piperazin-1-yl]methyl}phenol, 1-Cinnamylpiperazine, and Cinnamaldehyde.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Cinnarizine is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. No information is available on the use of cinnarizine during breastfeeding. Expert opinion recommends that cinnarizine not be used in migraine prophylaxis in nursing mothers. An alternate drug is preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

Cinnarizine is a N-alkylpiperazine, a diarylmethane and an olefinic compound. It has a role as an antiemetic, a histamine antagonist, a calcium channel blocker, a muscarinic antagonist, an anti-allergic agent, a H1-receptor antagonist and a geroprotector.
First synthesized by Janssen Pharmaceuticals in 1955, cinnarizine is an anti-histaminic drug mainly used for the control of vestibular disorders and motion sickness. Cinnarizine is a specific calcium channel blocker that primarily works on the central vestibular system to interfere with the signal transmission between vestibular apparatus of the inner ear and the vomiting centre of the hypothalamus. Cinnarizine could be also viewed as a nootropic drug because of its vasorelaxating abilities (due to calcium channel blockage), which happen mostly in brain. Combination use of cinnarizine with other nootropics, such as [piracetam] resulted in enhanced effect of boosting brain oxygen supply.
A piperazine derivative having histamine H1-receptor and calcium-channel blocking activity with vasodilating and antiemetic properties but it induces PARKINSONIAN DISORDERS.

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Drug Indication
For the treatment of vertigo/meniere's disease, nausea and vomiting, motion sickness and also useful for vestibular symptoms of other origins.

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Mechanism of Action
Cinnarizine inhibits contractions of vascular smooth muscle cells by blocking L-type and T-type voltage gated calcium channels. Cinnarizine has also been implicated in binding to dopamine D2 receptors, histamine H1 receptors, and muscarinic acetylcholine receptors.

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Pharmacodynamics
Cinnarizine is an antihistamine and a calcium channel blocker. Histamines mediate a number of activities such as contraction of smooth muscle of the airways and gastrointestinal tract, vasodilatation, cardiac stimulation, secretion of gastric acid, promotion of interleukin release and chemotaxis of eosinophils and mast cells. Competitive antagonists at histamine H1 receptors may be divided into first (sedating) and second (non-sedating) generation agents. Some, such as Cinnarizine also block muscarinic acetylcholine receptors and are used as anti-emetic agents. Cinnarizine through its calcium channel blocking ability also inhibits stimulation of the vestibular system.

C26H28N2

368.51

368.225

298-57-7

Cinnarizine-d8;1185242-27-6

1547484

White to off-white solid powder

1.1±0.1 g/cm3

509.2±38.0 °C at 760 mmHg

117-120ºC

229.8±14.6 °C

0.0±1.3 mmHg at 25°C

1.626

4.63

0

2

6

28

429

0

C1CN(CCN1C/C=C/C2=CC=CC=C2)C(C3=CC=CC=C3)C4=CC=CC=C4

DERZBLKQOCDDDZ-JLHYYAGUSA-N

InChI=1S/C26H28N2/c1-4-11-23(12-5-1)13-10-18-27-19-21-28(22-20-27)26(24-14-6-2-7-15-24)25-16-8-3-9-17-25/h1-17,26H,18-22H2/b13-10+

1-benzhydryl-4-[(E)-3-phenylprop-2-enyl]piperazine

Dimitronal; Stugeron; Cinnarizine

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)

DMSO : ~7.14 mg/mL (~19.38 mM)

Solubility in Formulation 1: ≥ 0.71 mg/mL (1.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 0.71 mg/mL (1.93 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 0.71 mg/mL (1.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 12 mg/mL (32.56 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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