Cyclizine (100 μM) dramatically reduced the levels of iNOS protein and LPS-stimulated nitrite buildup in RAW 264.7 cell supernatants [1]. With an IC50 of 5.42 µM, cyclidine prevents anti-IgE-induced histamine release from human lung fragments[2].

Mice's locomotor activity is enhanced by cycliclizine (1, 10 mg/kg) in a dose-dependent way [3].

Animal/Disease Models: Naive male CDI mice (Charles River), body weight 25-30 g[3]
Doses: 1, 10 mg/kg
Route of Administration: subcutaneous injection; measure locomotor activity (crossover) every 15 minutes for 2 hrs (hrs (hours)) .
Experimental Results: Enhanced locomotor activity in a dose-dependent manner.

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.

C18H22N2

266.38

266.178

82-92-8

Cyclizine dihydrochloride;5897-18-7;Cyclizine lactate;5897-19-8;Cyclizine hydrochloride;303-25-3

6726

White to off-white solid powder

105.5-107.5
105.5 TO 107.5 °C

2.899

0

2

3

20

253

0

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

NautazineCYCLIZINE Valoid Neo-devomitMarezine Ciclizina

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 : ~100 mg/mL (~375.40 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.39 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 25.0 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: ≥ 2.5 mg/mL (9.39 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 25.0 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: ≥ 2.5 mg/mL (9.39 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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