Disease relevance of Sibelium

• Flunarizine in alternating hemiplegia in childhood [1].
• Parkinsonism, tardive dyskinesia, akathisia, and depression induced by flunarizine [2].
• One woman presented with severe symptoms and 20 months after stopping flunarizine she still had dyskinesia and akathisia [2].
• Flunarizine: a once-daily therapy for urinary incontinence [3].
• Flunarizine allows differentiation between mechanisms of arrhythmias in the intact heart [4].

Psychiatry related information on Sibelium

• Flunarizine as maintenance treatment of a patient with bipolar disorder [5].
• In combination with appropriate behavioral analyses, photochemical thrombosis may constitute a relevant stroke model, in which flunarizine preserved behavioral function during a critical period, corresponding to the spread of ischemic damage [6].
• Cyclandelate versus flunarizine. A double-blind study in a selected group of patients with dementia [7].
• Further, flunarizine (10 and 20 mg/kg) potentiated the efficacy of carbamazepine and valproate against maximum electroshock (50 mA)-induced seizures and, in the dose of 20 mg/kg, enhanced that of diphenylhydantoin [8].
• Only flunarizine protected against the hypoxia-induced amnesia [9].

High impact information on Sibelium

• Systemically administered flunarizine enhanced neuronal survival in lumbar sensory ganglia in newborn rats after axotomy [10].
• Parkinsonism, tardive dyskinesia, akathisia, and depression induced by flunarizine [11].
• The vasodilating effects of flunarizine on smooth muscle strips of rabbit mesenteric artery have been investigated and compared with those of nifedipine [12].
• Mechanisms of flunarizine-induced vasodilation in the rabbit mesenteric artery [12].
• A comparative study of the diphenylpiperazines, cinnarizine and flunarizine, with the dihydropyridine, nifedipine, allows conclusions to be drawn as to their specificity of action [13].

Chemical compound and disease context of Sibelium

• To establish its value in differentiating between mechanisms of arrhythmias in the canine heart, the effect of flunarizine was investigated on ventricular tachycardia (VT) induced by ouabain intoxication or occurring 16-24 hours after occlusion of the left anterior descending coronary artery [4].
• When treatment with prostaglandin E2 was combined with simultaneous administration of either dazmegrel (UK 38,485, 50 mg/kg bodyweight) or Sibelium (Flunarizine R 14,950, 0.2 mg/kg body weight) a significant decrease in the mortality rate (p less than 0.05) was recorded [14].
• Functional, behavioral, and histological changes induced by transient global cerebral ischemia in rats: effects of cinnarizine and flunarizine [15].
• Diazepam, used clinically in the management of tonic-clonic status epilepticus, and flunarizine, a calcium channel blocker with anticonvulsant activity, potentiated [3H]phenytoin binding at micromolar concentrations [16].
• Rats and rabbits received topical flunarizine or vehicle before and after ischemia or NMDA [17].

Biological context of Sibelium

• Furthermore, both pharmacological inhibition and siRNA transfection of HO-1 completely abolished the flunarizine-mediated protection of HEI-OC1 cells and the primary rat (P2) organ of Corti explants from cisplatin [18].
• Flunarizine induces Nrf2-mediated transcriptional activation of heme oxygenase-1 in protection of auditory cells from cisplatin [18].
• Flunarizine inhibited serotonin uptake in a concentration dependent manner with an IC50 value of 1 mumol/L in blood platelets and 5 mumol/L in synaptosomes [19].
• At this dose, flunarizine had no effect on systemic blood pressure [20].
• Hemodynamic and metabolic effects of flunarizine in experimental subarachnoid hemorrhage in dogs [21].

Anatomical context of Sibelium

• Blood flow to primary tumors and lymph node metastases in SMT-2A tumor-bearing rats following intravenous flunarizine [22].
• The CyaA-mediated [Ca(2+)](i) increase in CD11b(+) J774A.1 monocytes was inhibited by extracellular La(3+) ions but not by nifedipine, SK&F 96365, flunarizine, 2-aminoethyl diphenylborinate, or thapsigargin, suggesting that influx of Ca(2+) into cells was not because of receptor signaling or opening of conventional calcium channels by cAMP [23].
• CONCLUSIONS: Flunarizine has a protective effect on neurological recovery after experimental ischemic spinal cord injury [24].
• Early (after the first blood injection) peroral treatment with flunarizine (0.5 mg/kg daily) resulted in less severe basilar artery narrowing (56% of normal; p < 0.05 versus untreated) [21].
• Protective effect of flunarizine on blood-brain barrier permeability alterations in acutely hypertensive rats [25].

Associations of Sibelium with other chemical compounds

• Epidermal growth factor-induced DNA synthesis was decreased by block of BK channels or by application of the Ca(2+) channel blockers nimodipine and flunarizine [26].
• The relaxation effect was cancelled out by the presence of adenosine as a cosolute in a dose-dependent fashion, leading to the suggestion that the endogenous mediator adenosine affects binding of flunarizine to the neutrophil surface [27].
• Using filtration and viscosity techniques, cyclandelate, some of its metabolites and flunarizine were evaluated to determine their ability to maintain human red blood cell (RBC) deformability [28].
• Studies were conducted on isolated rat retinas, cortical cultures, and brain synaptosomes to compare the effectiveness of flunarizine with nifedipine and betaxolol at reducing the influx of calcium or sodium [17].
• The potential of the calcium-entry blocker flunarizine in modulating the cytotoxicity of doxorubicin was investigated in human colon-adenocarcinoma cell lines sensitive to (LoVo) or with experimentally induced resistance (LoVo/DX) to doxorubicin [29].

Gene context of Sibelium

• Flunarizine also inhibits KCNQ1/KCNE1 channel current with an IC50 of 0.76 microM [30].
• Serum prolactin is increased during chronic flunarizine treatment of patients suffering from migraine [31].
• The effect of flunarizine on hERG potassium current is concentration and time dependent, and displays voltage dependence over the voltage range between -40 and 0 mV [30].
• Concomitant with an increase in viability, treatment with flunarizine resulted in a marked dissociation of Nrf2/Keap1 and subsequent intranuclear translocation of Nrf2, which was mediated by PI3K-Akt signaling [18].
• A paradoxical increase of growth hormone to thyrotropin releasing hormone observed before therapy was blunted after flunarizine treatment [32].

Analytical, diagnostic and therapeutic context of Sibelium

• Flunarizine protects neurons from death after axotomy or NGF deprivation [10].
• In cell culture, flunarizine at 30 to 40 microM also prevented neuronal death in nerve growth factor-dependent embryonic sensory and sympathetic neurons after the abrupt withdrawal of neurotrophic support [10].
• 12 subjects, 8 women and 4 men, presented with extrapyramidal motor signs and psychic depression after treatment with flunarizine for between 3 weeks and 15 months [2].
• Using 113Sn-labeled microspheres, 25 micron in diameter, we measured blood flow to primary tumors and regional lymph node metastases in conscious SMT-2A mammary adenocarcinoma-bearing syngeneic rats following a single i.v. bolus injection of the calcium entry blocker, flunarizine [22].
• After reperfusion the dogs received the calcium entry blocker, flunarizine, 6 micrograms/kg infused over a ten minute period [33].

References