Cinnarizine

Cinnarizine is an orally active, effective and selective inhibitor of L-type calcium channel Cav1.3 with an IC₅₀ of 1.5 μM (in vestibular hair cells). Cinnarizine can cross the blood-brain barrier and regulate calcium homeostasis and dopamine neurotransmission. Cinnarizine inhibits the influx of calcium ions into smooth muscle cells by blocking L-type calcium channels, thereby relaxing vascular smooth muscle, improving cerebral circulation and reducing blood viscosity, while antagonizing dopamine receptors. Cinnarizine can be used in the study of vestibular vertigo, Meniere's disease and cerebrovascular diseases^{[1][2][3][4][5]}. In Vitro:Cinnarizine (1.5 μM; transient treatment) inhibits L-type calcium current (I_Ca) in a concentration-dependent manner in the voltage-gated calcium current assay of guinea pig vestibular type II hair cells, and the reversibility decreases with increasing concentration^[1].
Cinnarizine (0.5 μM, 1 μM; transient treatment) significantly inhibits pressure-induced potassium current in the pressure-sensitive potassium current assay of guinea pig vestibular type II hair cells, and the inhibitory effect can be completely blocked by Charybdotoxin (HY-P0191)^[2].
Cinnarizine (1-30 μM; 24 h) stimulates HAC15 cells with angiotensin II, reduces aldosterone concentration and CYP11B2 expression^[3].
In Vivo:Cinnarizine (10 mg/kg; oral; once daily; 6 weeks) induces local hair loss and oral dyskinesia in the parkin knockout model (PK-KO) of female mice, significantly reduced the motor activity of mice, and enhanced striatal dopamine metabolism and compensatory activation of the glutathione system^[4].
Cinnarizine (2-10 mg/kg; intravenous injection; once daily; 30 days) has a dose-dependent pharmacokinetic profile in beagle dogs, causing reversible renal injury at 10 mg/kg, with a significant cumulative effect^[5].