RESEARCH MONOGRAPH · KDC-MN-309

Cinnarizine

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

71/100

The dual-action calcium blocker and antihistamine thats been in Europe since the 50s, mostly used for motion sickness but the cerebrovascular use is still real

Cinnarizine is one of those workhorse molecules thats been around for so long the pharmacology has become both well-understood and slightly underappreciated. Developed by Janssen in 1955, it's a diphenylmethyl-piperazine with two mechanistically distinct primary effects: L-type calcium channel antagonism (particularly cerebral vascular smooth muscle) and H1-histamine receptor antagonism. The combination produces vestibular suppression for the motion sickness indication and cerebrovascular vasodilation for the cognitive/cerebrovascular indication, plus some incidental sedation from the H1 effect.

The clinical evidence is genuinely substantial across motion sickness, vestibular disorders (particularly Meniere's-related vertigo), and cerebrovascular indications. The motion sickness data is among the strongest of any antiemetic class for the specific indication. The cerebrovascular and cognitive trials are more modest in effect size but the Sibelium (flunarizine, a fluorinated cinnarizine analog) data adds context for the class.

What's interesting about cinnarizine is the calcium channel selectivity profile. It's not a particularly potent CCB in cardiovascular terms, but it has a meaningful preference for the cerebrovascular L-type channels over the systemic ones, which gives you the cerebrovascular effect at doses that dont produce significant systemic hypotension. That selectivity is one of the older examples of tissue-selective ion channel pharmacology that informed later channel selectivity work.

What we like: long safety record, well-characterized dual mechanism, and a useful research tool for cerebrovascular and vestibular pharmacology. The motion sickness pharmacology is genuinely the best in class for prophylactic use.

What we dont love is the extrapyramidal symptoms tail. Cinnarizine (and more so flunarizine) has dose-dependent D2 dopamine antagonism that can produce parkinsonian symptoms and tardive movement effects with chronic use. The risk is small at short-term doses but real with extended exposure, and the case literature is well-documented enough that the chronic-use indications have been progressively restricted in some markets.

Sourcing is excellent. Cinnarizine is pharma-grade, USP-monographed in some pharmacopoeias, dirt cheap, and reliably available. HPLC purity is straightforward, the molecule is stable, and the failure modes are minimal.

Evidence: 70
Mechanism: 75
Reliability: 70
Safety: 65
Sourcing: 85
Value: 80
Signal: 55
Staying power: 65

Plain-language summary Intrigue 42 / 100

Cinnarizine is a 1970s Janssen compound that hits multiple targets at once: T-type calcium channels (cerebrovascular dilation, vestibular nerve effects), H1 histamine receptors (antihistamine), and weakly D2 dopamine receptors. The combined activity makes it useful for vertigo, motion sickness, and cerebrovascular insufficiency. Approved across Europe and Asia, never in the US. The D2 antagonism produces a small but real risk of drug-induced parkinsonism with long-term use, especially in elderly patients, which has limited enthusiasm. The motion sickness use is well-established. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Diphenylmethyl-piperazine calcium channel blocker / antihistamine

A diphenylmethyl-piperazine T-type calcium channel blocker with antihistamine activity; used for vertigo, motion sickness, and cerebrovascular disease.

Abstract

Cinnarizine (1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)piperazine; CAS 298-57-7; molecular formula C26H28N2; molecular weight 368.52) is a diphenylmethyl-piperazine multi-target compound developed at Janssen and approved in many European and Asian markets in the 1970s. Mechanism: T-type voltage-gated calcium channel inhibition (cerebrovascular dilation, vestibular nerve effects), H1 antihistamine activity, and weak D2 dopamine receptor antagonism. The combined activity supports use in vestibular disorders, motion sickness, and cerebrovascular insufficiency. The D2 antagonism produces a small but real risk of extrapyramidal side effects (parkinsonism, tardive dyskinesia) with long-term use, particularly in elderly patients; this has limited use in some jurisdictions. Plasma half-life is approximately 4 hours. Approved for vertigo, motion sickness, and cerebrovascular disease in EU and Asia; not approved in the US. Used as a multi-target reference compound for vestibular pharmacology.

Mechanism of action

T-type calcium channel inhibition, H1 antihistamine, weak D2 antagonism. Multi-target activity supports vertigo and cerebrovascular indications.

Reported research dose ranges

Clinical 25 to 75 mg in the published literature.

References

Pianese CP, et al. Cinnarizine for vertigo: a review. Eur Arch Otorhinolaryngol 2005.
Fraga JL, Cabrera J. Adverse effects of cinnarizine in the published literature. Drug Saf 1995.
Holguin J, et al. Cinnarizine in motion sickness. Aviat Space Environ Med 1979.

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KDC-MN-309

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

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Cinnarizine

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Mechanism of action

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Abstract

Mechanism of action

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References

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