Cinnarizine

Cinnarizine is an antihistamine and calcium-channel blocker that was first synthesized as an antivertigo/anti-motion sickness medication. The anti-emetic mechanism involves histamine H₁ and muscarinic receptor antagonism in vestibular nuclei and the brainstem vomiting center as well as blockade of L- and T-type Ca²⁺ channels which influence labyrinthine and gastrointestinal sensory afferents. By inhibiting vestibular hyperexcitability and gastrointestinal smooth-muscle spasms, the drug prevents the inappropriate convergence of conflicting sensory inputs that cause nausea and vomiting.
In contrast to dopamine or 5-HT₃ antagonists, it is ineffective against cytotoxic- or apomorphine-induced emesis, which has demonstrated a restricted, vestibular-predominant spectrum.

Fig. 1 Human vomiting defense mechanism. (Sanger G J.; et al. 2018)

Cinnarizine improves cerebral blood flow, is almost insoluble at physiological pH and therefore orally erratic. Zhang Y et al. prepared fast-dissolving poly-vinyl-pyrrolidone K90 microneedle arrays (15×15 needles, 840 µm long) loaded with 3 mg cinnarizine per patch. After neck application on rats for 20 min the micro-cones completely dissolved, delivering ≈70 % of the dose within 1 h. Ethanol residue was negligible and no local or systemic toxicity was observed. LC-MS/MS analysis demonstrated that although intravenous cinnarizine reached higher systemic Cmax, the intradermal patch gave a brain-targeting index of 1.85, almost doubling the AUCbrain/AUCblood ratio. The simple, solvent-cast, UV-cured patch is thus a safe, scalable and user-friendly platform that converts the poorly bioavailable drug into an effective neuro-protective agent against Microwave-induced brain injury (MIBI) by simultaneously limiting calcium excitotoxicity and neuro-inflammation.

Fig. 2 Fabrication of Cinnarizine microneedles. (Zhang Y.; et al. 2022)