Drug-induced parkinsonism: cinnarizine and flunarizine are potent uncouplers of the vacuolar H+-ATPase in catecholamine storage vesicles

  title={Drug-induced parkinsonism: cinnarizine and flunarizine are potent uncouplers of the vacuolar H+-ATPase in catecholamine storage vesicles},
  author={Ole Terland and Torgeir Flatmark},
Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine
It is suggested that cinnarizine improves the haloperidol induced brain oxidative stress and impairment of learning and memory in the water maze test in mice.
Effect of Verapamil, Cinnarizine and Memantine on Maximal Electroshock, Picrotoxin, and Pilocarpine-Induced Seizure Models in Albino Mice
Assessment of effects of verapamil, cinnarizine and memantine on experimentally induced convulsions in albino mice found the drug potentiated seizure occurrence in pilocarpine model.
Modulation of Visceral Nociception, Inflammation and Gastric Mucosal Injury by Cinnarizine
It is suggested that cinnarizine exerts anti-inflammatory, antinociceptive and gastric protective properties and is likely to involve adenosine receptors and KATP channels.
LC-MS/MS method development and validation of an antihistaminic, calcium channel blocker, di-phenyl-methyl-piperazine group containing cinnarizine in human plasma with an application to BA/BE studies in Indian volunteer
T attempts were made to develop and validate a bioanalytical method for the determination and quantitation of the cinnarizine in human plasma by liquid chromatography-mass spectrometric method and the developed method was also applied to analyse the plasma samples of healthy human volunteers obtained from a comparative pharmacokinetic study of cinnARizine 25mg tablet dosage forms.
Effects of cinnarizine on calcium and pressure-dependent potassium currents in guinea pig vestibular hair cells
It is concluded that cinnarizine inhibits, by two mechanisms, pressure-induced currents that are sensitive to charybdotoxin and Ca2+.
Three-dimensional hydrogen-bonded framework structures in flunarizinium nicotinate and flunarizinediium bis(4-toluenesulfonate) dihydrate.
The structures of two salts of flunarizine, namely 1-bis[ (4-fluorophenyl)methyl]-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine-1,4-diium bis(4-methylbenzenesulfonate) dihydrate, are reported and Comparisons are made with some related structures.
Neuroprotective Strategies in Parkinson’s Disease
In spite of the extensive studies performed on postmortem substantia nigra from Parkinson’s disease patients, these studies have demonstrated that, at the time of death, a cascade of events had been initiated that may contribute to the demise of the melanin-containing nigro-striatal dopamine neurons.


Flunarizine and cinnarizine inhibit mitochondrial complexes I and II: possible implication for parkinsonism.
In intact mitochondria from rat liver, both drugs inhibited respiration rates, with substrates entering at Complex I (glutamate/malate) and Complex II (succinate) and these effects could be explained by potent inhibitions of both complexes.
The effect of prenylamine and organic nitrates on the bioenergetics of bovine catecholamine storage vesicles.
D2 Receptor Blockade by Flunarizine and Cinnarizine Explains Extrapyramidal Side Effects. A SPECT Study
  • T. Brücke, C. Wöber, L. Deecke
  • Medicine, Psychology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 1995
Findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects, and older age and long-term treatment are predisposing factors for these effects.
Effects of calcium antagonists on biogenic amines in discrete brain areas.
Dopamine oxidation generates an oxidative stress mediated by dopamine semiquinone and unrelated to reactive oxygen species.
Dopamine (100 microM, 10-30 min) inhibits/inactivates the MgATP-dependent generation of a transmembrane proton electrochemical gradient in chromaffin granule ghosts, indicating that the toxic metabolite (dopamine semiquinone) inhibits proton pumping by inhibiting the endogenous vacuolar H(+)-ATPase.
Effects of calcium antagonists on the dopamine system.
The finding of dopamine-regulating properties not associated to neurotoxic effects in the dihydropyridines and verapamil provides new putative therapeutics tools for the treatment of neurologic disorders associated with dopamine hyperactivity.
Studies on Mg2+-dependent ATPase in bovine adrenal chromaffin granules. With special reference to the effect of inhibitors and energy coupling.
ADP was found to be a potent inhibitor of the proton pump activity with MgATP as the substrate, and the effect can partly be explained by a competitive type of inhibition of the hydrolytic reaction.
Flunarizine. A reappraisal of its pharmacological properties and therapeutic use in neurological disorders.
Flunarizine is useful in the prophylaxis of migraine, an effective treatment for vertigo and a worthwhile alternative as 'add-on' therapy in patients with epilepsy resistant to conventional drugs.