flunarizine and Hyperventilation

The effect of flunarizine (10 mg/day) was studied in open and double-blind clinical trials. Patients presenting the symptom of dizziness were diagnosed as having the hyperventilation syndrome. They showed vestibular hyperreactivity in the velocity step test. This test was performed before and after 4-6 weeks of treatment. The results of treatment were compared with a control or placebo group. In an open trial, 12 of 14 patients reported alleviation of dizziness during treatment and showed a significant decrease in right-left asymmetry of their velocity step responses. In a double-blind trial, no significant difference in effects or side effects was found between the drug and placebo groups.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Dizziness; Double-Blind Method; Electronystagmography; Female; Flunarizine; Humans; Hyperventilation; Male; Middle Aged; Reflex, Vestibulo-Ocular; Syndrome; Vestibular Function Tests

Flunarizine (10 mg/day) was given in an open pilot study to 14 patients with the primary complaint of dizziness, who showed vestibular hyperreactivity in the velocity step (VS) test and were proven to have a hyperventilation syndrome (HVS) without any other disease. The VS test was repeated after 4-6 weeks of treatment. Twelve of these HVS patients reported alleviation of dizziness. Objective evaluation of the results of treatment was attempted by defining suitable response parameters and comparing their values to those obtained in a control group of 14 healthy volunteers tested twice with the same interval. A significant decrease in right-left asymmetry in the VS responses of the patients on drug was found.

Topics: Adolescent; Adult; Aged; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Dizziness; Female; Flunarizine; Humans; Hyperventilation; Male; Middle Aged; Vestibular Function Tests; Vestibule, Labyrinth

Dotarizine and Flunarizine are piperazine derivatives considered to be effective compounds for the treatment of various cerebrovascular disorders. In the present study the influence of these two drugs on changes in cerebral vessel diameter and blood flow velocity were measured and compared utilising transcranial Doppler sonography during hyperventilation in anaesthetized cats. Drugs were administered in 15 min intravenous infusions at a dose of 0.05 mg/kg/min. This investigation revealed that the 15 min intravenous administration of both compounds abolished the cerebral vasoconstrictor effects of hyperventilation and due to vasodilator effects they increased blood flow velocity to initial values. No statistically significant differences were found between the vasodilator effects of Dotarizine and Flunarizine. Results obtained suggest that Dotarizine, a novel piperazine derivative, has similar vasodilator and Ca2+ channel blocking effects on cerebrovascular reactivity compared to the widely clinically applied Flunarizine.

Topics: Animals; Benzhydryl Compounds; Blood Flow Velocity; Blood Pressure; Calcium Channel Blockers; Cats; Cerebrovascular Circulation; Flunarizine; Hyperventilation; Male; Piperazines; Vasoconstriction

Flunarizine is a calcium entry blocking drug possessing antihypoxic activity in animal models of cerebral and peripheral ischemia-anoxia and has clinical usefulness in circulatory disorders of both central and peripheral origin. This report compares the activity of flunarizine and verapamil, another calcium entry blocking drug, on the central nervous system (CNS) and peripheral consequences of cytotoxic hypoxia induced by high and low doses of KCN. The lethal effect of KCN (6 mg/kg, i.p.) in rats was prevented by orally administered flunarizine (ED50 = 12 mg/kg with four-hr pretreatment) but not by verapamil (at oral doses up to 80 mg/kg with one-hr pretreatment). Since the lethal effect of KCN involves failure of respiration at the CNS level, these results suggest that flunarizine protects against the hypoxic effect of the cyanide ion by an action in brain tissue. We found also that the stimulant effect of low intravenous doses (0.5 mg/kg/min) of KCN upon respiration rate was not altered in pentobarbital- and chloralose-anesthetized rats treated with oral doses of flunarizine up to 80 mg/kg (with four hr pretreatment). In contrast, KCN-stimulated respiration rate in pentobarbital anesthetized rats was significantly attenuated by verapamil (20 and 40 mg/kg, p.o. with one hr pretreatment). Since low doses of the cyanide ion render respiration quicker and deeper by an action on chemoreceptive cells in peripheral arteries, the effect of verapamil against the hypoxic effect of KCN is mediated by an action in the periphery. In summary, we have shown that the physiological consequences of cytotoxic hypoxia can be affected by calcium entry blocking drugs having site-specific activities. Based on our results, flunarizine is more effective than verapamil against cellular anoxia involving the CNS.

Topics: Animals; Calcium Channel Blockers; Cinnarizine; Flunarizine; Hyperventilation; Hypoxia; Male; Piperazines; Potassium Cyanide; Rats; Rats, Inbred Strains; Verapamil