Cinnarazine

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Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. It is also known to promote cerebral blood flow. It is not available in the United States or Canada.

Pharmacodynamics[edit | edit source]

The following information is a partial reprint of the Wikipedia article on cinnarizine:

"Cinnarizine is classified as a selective antagonist of T-type voltage-operated calcium ion channels, because its binding blocks the channels and keeps them inert.[1][2] It has a Ki (inhibitory constant) value of 22nM.[3] It is also known to have antihistaminic, antiserotoninergic and antidopaminergic effects,[2] binding to H1 histamine receptors, and dopaminergic (D2) receptors.[4] The IC50 (half-maximal inhibitory concentration) of cinnarizine for smooth muscle contraction inhibition is 60mM[5] and it has been shown that this drug preferentially binds to its target calcium channels when they are in an open, as opposed to closed conformation.[6] In treatment of nausea and motion sickness it was previously hypothesized that cinnarizine exerts its effects by inhibiting the calcium currents in voltage gated channels in type II vestibular hair cells within the inner ear.[7] However, more recent evidence supports the idea that at pharmacologically relevant levels (0.3µM–0.5µM), cinnarizine is not lessening vestibular vertigo by blocking calcium channels, but rather by inhibiting potassium (K+) currents that are activated by heightened hydrostatic pressure on the hair cells.[8] It is true that cinnarizine does abolish calcium currents in vestibular hair cells as well; it is just that this only occurs at higher concentrations of drug (3µM).[8] The inhibition of these currents works to lessen the vertigo and motion-induced nausea by dampening the over-reactivity of the vestibular hair cells, which send information about balance and motion to the brain."[9]
Action of cinnarizine Target of action
Calcium ion channel antagonist T-type calcium channels
Antihistaminic H1 receptors
Antiserotinergic 5-HT2 receptors[10]
Antidopaminergic D2 receptors

References[edit | edit source]

  1. Deka, C.V.R. (2006). "Role of Cinnarizine in Peripheral Vertigo". Vertigo Viewpoint. 4 (1): 2–4. 
  2. 2.02.1 Fabiani G, Pastro PC, Froehner C (September 2004). "Parkinsonism and other movement disorders in outpatients in chronic use of cinnarizine and flunarizine". Arquivos de Neuro-Psiquiatria. 62 (3B): 784–8. doi:10.1590/S0004-282X2004000500008. PMID 15476069. 
  3. Klein M, Musacchio JM (October 1989). "High affinity dextromethorphan binding sites in guinea pig brain. Effect of sigma ligands and other agents". The Journal of Pharmacology and Experimental Therapeutics. 251 (1): 207–15. PMID 2477524. 
  4. Kariya S, Isozaki S, Masubuchi Y, Suzuki T, Narimatsu S (November 1995). "Possible pharmacokinetic and pharmacodynamic factors affecting parkinsonism inducement by cinnarizine and flunarizine". Biochemical Pharmacology. 50 (10): 1645–50. doi:10.1016/0006-2952(95)02057-8. PMID 7503767. 
  5. Silver PJ, Dachiw J, Ambrose JM, Pinto PB (September 1985). "Effects of the calcium antagonists perhexiline and cinnarizine on vascular and cardiac contractile protein function". The Journal of Pharmacology and Experimental Therapeutics. 234 (3): 629–35. PMID 3162016. 
  6. López MG, Moro MA, Castillo CF, Artalejo CR, García AG (March 1989). "Variable, voltage-dependent, blocking effects of nitrendipine, verapamil, diltiazem, cinnarizine and cadmium on adrenomedullary secretion". British Journal of Pharmacology. 96 (3): 725–31. doi:10.1111/j.1476-5381.1989.tb11874.x. PMC 1854390Freely accessible. PMID 2720300. 
  7. Arab, Sonja F.; Düwel, Philip; Jüngling, Eberhard; Westhofen, Martin; Lückhoff, Andreas (Jun 1, 2004). "Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine". Naunyn-Schmiedeberg's Archives of Pharmacology. 369 (6): 570–575. doi:10.1007/s00210-004-0936-3. ISSN 0028-1298. 
  8. 8.08.1 Haasler T, Homann G, Duong Dinh TA, Jüngling E, Westhofen M, Lückhoff A (December 2009). "Pharmacological modulation of transmitter release by inhibition of pressure-dependent potassium currents in vestibular hair cells". Naunyn-Schmiedeberg's Archives of Pharmacology. 380 (6): 531–8. doi:10.1007/s00210-009-0463-3. PMID 19830405. 
  9. "Cinnarizine". Wikipedia. Sep 16, 2019. 
  10. Pukhal'skaya TG, Kolosova OA, Men'shikov MY, Vein AM (July 2000). "Effects of calcium antagonists on serotonin-dependent aggregation and serotonin transport in platelets of patients with migraine". Bulletin of Experimental Biology and Medicine. 130 (7): 633–5. doi:10.1007/BF02682090. PMID 11140571. 

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