cinnarizine and Hyperventilation

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

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