Disease relevance of cinnarizine

• The effect of 25 and 50 mg cinnarizine on seasickness severity was examined in 95 subjects during a voyage in rough seas [1].
• Flunarizine and cinnarizine inhibit mitochondrial complexes I and II: possible implication for parkinsonism [2].
• Cinnarizine markedly improved the functional abnormalities of ischemia but had little or no effect upon the neuronal damage [3].
• A small number of comparative studies have shown flunarizine to be at least as effective as pizotifen in migraine prophylaxis, and in a longer term study as effective as cinnarizine in vertigo of central origin [4].
• Cinnarizine-induced cholestasis [5].

Psychiatry related information on cinnarizine

• On IP administration, verapamil and cinnarizine (10, 20 and 40 mg/kg) given on eight occasions at an interval of 12 h reversed the withdrawal-induced increase in spontaneous motor activity [6].
• Promethazine and cinnarizine significantly impaired psychomotor performance, information processing and feelings of alertness [7].
• A total of 60 young naval crew (20 for dimenhydrinate, 15 for cinnarizine and 25 for transdermal scopolamine) underwent a battery of computerized and paper and pencil performance tests, and filled out a questionnaire on side-effects and well-being self-assessment [8].
• The most frequently reported were drowsiness or lethargy affecting 16 patients on cinnarizine and 7 on betahistine [9].
• Effect of pre-electroconvulsive shock (ECS) administration of calcium channel blockers (CCBs) like verapamil, diltiazem, nifedipine, nimodipine, flunarizine and cinnarizine on retrograde amnesia induced by ECS was examined using passive avoidance paradigm in rats [10].

High impact information on cinnarizine

• In NCB -20 cells, this voltage-sensitive 45Ca2+ uptake was inhibited selectively by organic calcium antagonists such as nitrendipine, cinnarizine, verapamil, and diltiazem (IC50 values = 6.4, 750, 1800, and 4500 nM, respectively) [11].
• Twenty-six patients under treatment with the calcium channel blockers flunarizine (Fz) or cinnarizine (Cz) were examined-with single-photon emission computed tomography using [123I]iodobenzamide as a ligand [12].
• D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side effects. A SPECT study [12].
• The effects of 25 mg cinnarizine on the vestibulo-ocular reflex were investigated in 13 subjects [1].
• The diphenylalkylamine calcium channel antagonists, lidoflazine, cinnarizine, flunarizine, and prenylamine, however, show a 3- to 10-fold increase in affinity in skeletal muscle relative to the other three tissues [13].

Chemical compound and disease context of cinnarizine

• These spasms were inhibited by calcium entry blockers with a rank order of potency of nifedipine = gallopamil greater than diltiazem greater than cinnarizine [14].
• At the same time, following the results obtained in FSIF tests and locomotor activity tests, it can be inferred that the 5-HT antagonists used (methysergide, cyproheptadine, metergoline, cinnarizine, and pizotifen) do not act specifically in this model of aggression [15].
• Effects of cinnarizine, a calcium antagonist that produces human parkinsonism, in parkin knock out mice [16].
• Comparison of cinnarizine, cyproheptadine, doxepin, and hydroxyzine in treatment of idiopathic cold urticaria: usefulness of doxepin [17].
• Subacute cutaneous lupus erythematosus associated with cinnarizine and thiethylperazine therapy [18].

Biological context of cinnarizine

• The inhibition of lipid peroxidation by cinnarizine. Possible implications to its therapeutic and side-effects [19].
• Both perhexiline and cinnarizine inhibited arterial myosin P-light chain phosphorylation and superprecipitation of arterial actomyosin over the concentration range of 10 to 200 microM [20].
• The IC50 values for inhibiting the generation of the membrane potential were even lower, i.e. 0.19+/-0.06 microM (n = 6) and 0.15+/-0.01 microM (n = 4) for cinnarizine and flunarizine, respectively [21].
• Prior to ligation, a sustained fall in mean arterial blood pressure was observed only following the administration of the highest doses of prenylamine, flunarizine and cinnarizine [22].
• Initial experiments giving the compounds at 50 mg kg-1 i.p. indicated that cinnarizine had no effect on cell survival after 20 Gy of X-rays in the RIF-1 sarcoma and only a small effect in the SCCVII/St carcinoma [23].

Anatomical context of cinnarizine

• 3 The calcium entry blocking drugs, cinnarizine and flunarizine, had little effect on the resting exchange of calcium in the arterial smooth muscle, but inhibited PGF2 alpha-stimulated contractions and 45Ca uptake to a similar extent [24].
• Oxidative metabolism of cinnarizine in rat liver microsomes [25].
• These results support the hypothesis that nifedipine, gallopamil, diltiazem and cinnarizine inhibit Ca2+- and KCl-induced tension development of rat uterus by reduction of Ca2+ influx [14].
• Our aim was to clarify whether cinnarizine affected voltage-dependent Ca2+ currents in vestibular type II hair cells [26].
• Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine [26].

Associations of cinnarizine with other chemical compounds

• Whereas ( +/- )-nitrendipine very potently displaced (+)-[3H]PN200-110 binding (IC50 = 1.3 nM) verapamil and cinnarizine displaced the binding by only 30 and 40% at 1 microM, and diltiazem increased it by 20% at 10 microM [27].
• In addition, the increase in ACh release induced by SS-14 or SS-28 was antagonized by the calcium channel antagonists omega-conotoxin GVIA, nifedipine, and cinnarizine, implicating voltage-sensitive calcium channels in this effect [28].
• However, whereas inhibition of superprecipitation and P-light chain phosphorylation by W-7 was equal at different Mg++ concentrations, relatively greater inhibition with perhexiline and less inhibition with cinnarizine was apparent as the free Mg++ concentration was lowered [20].
• An oral combination of cinnarizine and lorazepam was studied for the prophylaxis of nausea and vomiting induced by strongly emetogenic cancer chemotherapy [29].
• Ca++ antagonists, nonselective for slow Ca++ channels (flunarizine, cinnarizine, lidoflazine, prenylamine and bepridil) inhibited veratridine-induced release of LDH with IC50 values between 0.11 and 0.47 microM [30].

Gene context of cinnarizine

• Despite the effects of PACAP on IP3 production, the Ca2+ release induced by PA-CAP38 or by PACAP27 was unaffected by cinnarizine, a blocker of IP3 channels [31].
• Oxidative metabolism of flunarizine and cinnarizine by microsomes from B-lymphoblastoid cell lines expressing human cytochrome P450 enzymes [32].
• The antioxidant activity of cinnarizine may contribute to explain some of the effects of this drug [19].
• Cinnarizine (10 microM) increased the MgATPase activity of the granule ghosts by 47+/-26% (n = 4) compatible with an uncoupling of the vacuolar H+-ATPase activity [21].
• Perfusion with cinnarizine (50 microM) or dantrolene (10 microM), antagonists of the IP(3)R and RyR, respectively, eliminated the Ca(2+) response to microinjected IP(3) and cADPr [33].

Analytical, diagnostic and therapeutic context of cinnarizine

• The absolute bioavailabilities (Fabs) of cinnarizine after oral administration as two modified beta-cyclodextrin (SBE4-beta-CD or HP-beta-CD) solutions, an aqueous suspension, and two capsules in fasted beagle dogs were determined [34].
• Determination of cinnarizine in plasma by high-performance liquid chromatography [35].
• Blood samples were drawn for 24.5 h postdosing, and cinnarizine levels in plasma were determined by HPLC with spectrofluorometric detection [34].
• Plasma cinnarizine levels resulting from oral administration as capsule or tablet formulation investigated by gas-liquid chromatography [36].
• Cinnarizine has an atypical antipsychotic profile in animal models of psychosis [37].

References