flunarizine and Brain-Diseases

The present paper discusses the possible central effects of calcium antagonists on the central nervous system in the light of present knowledge of the role of Ca2+ in physiological and pathophysiological processes.

Topics: Animals; Brain; Brain Diseases; Calcium Channel Blockers; Calcium Channels; Flunarizine; Humans; Synapses

Rat models of the acute and recuperative phases of hypoxic ischemic encephalopathy (HIE) were established beginning by the 7th day after birth through ischemia and hypoxia. The prophylatic and therapeutic effects on experimental HIE were studied by the application of radix salviae miltiorrhizae, flunarizine and hyperbaric oxygen. Experimental data indicated that among these measures, radix salviae miltiorrhizae gave a better result and the pathological change in the prophylactic and therapeutic groups particularly the result of the latter one were light serious than those of the control group.

Topics: Animals; Atrophy; Brain; Brain Diseases; Calcium Channel Blockers; Drugs, Chinese Herbal; Flunarizine; Hypoxia; Organ Size; Plant Extracts; Rats; Rats, Wistar; Salvia miltiorrhiza; Vasodilator Agents

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. The striatal dopamine D2 receptor-binding potential was determined and found to be reduced by 14 to 63% (39.5 +/- 15.0%; p < 0.0001) in patients compared with age-matched control values. This reduction was larger in 12 patients with extrapyramidal symptoms and was only slowly reversible after discontinuation of treatment. Patients treated for > 6 months had significantly larger reductions than patients treated for a shorter period. Parkinsonian symptoms were only seen in patients older than 50 years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects. Older age and long-term treatment are predisposing factors for these effects.

Topics: Adult; Aged; Brain Diseases; Cinnarizine; Dopamine D2 Receptor Antagonists; Female; Flunarizine; Humans; Male; Middle Aged; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

Calcium antagonist therapy has been reported to reduce neuronal death after hypoxia-ischemia; however, its potential use in prenatal hypoxic-ischemic events has received little attention. We examined the effect of pretreatment with flunarizine in chronically instrumented late gestation fetal sheep subjected to 30 min of cerebral ischemia. Eight fetuses were given 0.11 mmol (45 mg) of flunarizine over 2 h preischemia (high dose), 10 were given 0.07 mmol (30 mg) over 3 h preischemia (low dose), 17 were given nothing (ischemia controls), and 5 received neither the ischemic insult nor any treatment (sham controls). The fetal electrocorticogram was monitored for 3 d postinsult. Histologic outcome was quantified after 72 h. Low-dose, but not high-dose, flunarizine therapy was associated with an overall reduction in cerebral damage (p < 0.01), a greater final electrocorticogram intensity, and a reduction in the incidence of seizures (p < 0.02) compared with ischemia controls. High-dose, but not low-dose, flunarizine was associated with a significant acute mortality and a decrease in fetal blood pressure (p < 0.05) at the time of occlusion, although there was no effect on the initial hypertensive response to occlusion. These observations suggest that flunarizine is partially neuroprotective when given before severe global ischemia in utero, but that its hypotensive effects make it unsuitable for prophylactic administration in utero.

Topics: Animals; Brain Diseases; Brain Ischemia; Calcium Channel Blockers; Disease Models, Animal; Female; Fetal Hypoxia; Flunarizine; Hypotension; Hypoxia, Brain; Pregnancy; Sheep

Alterations in regional cerebral blood-flow, as determined by single-photon emission computed tomography (SPECT) using technetium [99mTc] hexamethyl propylenamine oxime, were studied in two children presenting with alternating hemiplegia of childhood. Both experienced hemiplegic episodes several times per month, despite marked improvement on flunarizine therapy. SPECT images of both patients revealed focal areas of decreased uptake of the radiotracer, representing impaired regional cerebral blood-flow during, as well as between, seizures. The interictal finding of localized areas of reduced tracer uptake suggest that long-lasting hypoperfusion could be the pathophysiological mechanism by which the slowly resolving hemiplegia, and ultimately the permanent multifocal neurological deficits, are produced.

Topics: Brain; Brain Diseases; Cerebrovascular Circulation; Child, Preschool; Female; Flunarizine; Functional Laterality; Hemiplegia; Humans; Intellectual Disability; Language Disorders; Male; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

One postulated final common pathway leading to neuronal death after hypoxic-ischemic insults is an increase in intracellular calcium concentrations. We examined the effect of pretreatment with flunarizine, a calcium channel antagonist known to pass the blood brain barrier, on the behavioral and histologic changes after an hypoxic-ischemic insult in the infant rat. The 21-d-old rats were subjected to unilateral carotid ligation, then to 2 h of hypoxia. They were pretreated with either flunarizine (30 mg/kg, intraperitoneally) or with an equal volume of diluent. After 5 days of observation they were killed for histology. Acute behavioral abnormalities were observed in more controls than treatment animals, 52 vs 11% (p less than 0.002). Cerebral injury was almost entirely confined to the ligated side and was significantly worse in the control rats. Full thickness cortical infarction was noted in 56% of controls (n = 27) vs 4% of flunarizine-treated rats (n = 24), (p less than 0.001). Mean and maximum damage scores for all areas assessed including cortex, corpus striatum, thalamus, amygdala, and hippocampus were improved markedly in treatment rats (p less than 0.005). These observations confirm that flunarizine, when given prophylactically, has a neuroprotective effect against hypoxic-ischemic injury in the developing brain.

Topics: Animals; Animals, Newborn; Brain Diseases; Brain Ischemia; Flunarizine; Hypoxia; Rats

A new classification of calcium antagonists has been developed by a WHO expert committee. Substances acting primarily via the inhibition of calcium entry into the cell have been divided into four distinct classes. The pharmacological characteristics of these classes that may be relevant for the use in various neurological disorders are highlighted in this paper. Some main differences concern the effects on vascular smooth muscle cells and brain cells. The well-documented clinical applications in neurology are still limited to migraine prophylaxis and vertigo. The evidence concerning the usefulness in cerebral vasospasm secondary to subarachnoid haemorrhage was regarded as reasonable, whereas several neurological indications should still be regarded as being under examination. There is little doubt that calcium antagonists will gain importance in the treatment of several neurological diseases.

Topics: Brain Diseases; Calcium Channel Blockers; Diltiazem; Flunarizine; Humans; Nifedipine; Verapamil

Cinnarizine and flunarizine are selective calcium blockers that have been used to treat and prevent vertigo. We studied 15 patients who had extrapyramidal syndromes after taking these drugs. Eleven patients had parkinsonism, one with persistent akathisia as well; one had an orofacial tremor; one, acute akathisia alone; and one an acute dystonic reaction. All but one improved when the drug therapy was discontinued. Seven patients were also depressed during treatment. Cinnarizine and flunarizine must therefore be added to the list of potentially risky drugs known to induce extrapyramidal reactions and depression.

Topics: Adult; Aged; Aged, 80 and over; Brain Diseases; Cinnarizine; Female; Flunarizine; Humans; Male; Middle Aged; Movement Disorders; Parkinson Disease, Secondary; Pyramidal Tracts

A 10-minute cardiac arrest was produced in dogs by electrical fibrillation of the heart. Recovery of cerebral function was monitored by estimating the cerebral metabolic rate of oxygen consumption (CMRO2), cerebral blood flow (CBF), electroencephalograph (EEG) and extent of neurological deficit. The study group received flunarizine (0.1 mg/kg intravenously) at the beginning of resuscitation, while control animals were given the drug vehicle. By four hours after resuscitation, CMRO2 in flunarizine-treated dogs was 121 +/- 43% of pre-arrest baseline, as compared with 37 +/- 9% in control animals (P less than 0.02). In the flunarizine group, CBF was 83 +/- 21% of baseline, while it was only 31 +/- 8% in controls (P less than 0.01). As compared with the control group, no other significant changes were detected in electrocardiographic, hemodynamic, or biochemical parameters in the flunarizine-treated dogs. A significant improvement in the visual EEG score (P less than 0.001) and neurological deficit (P less than 0.05) was seen in flunarizine-treated dogs six hours after ischemic insult.

Topics: Animals; Brain; Brain Diseases; Cerebrovascular Circulation; Cinnarizine; Dogs; Electrocardiography; Electroencephalography; Flunarizine; Heart Arrest; Oxygen Consumption; Piperazines; Resuscitation