cinnarizine and Epilepsy

Topics: Adolescent; Adult; Calcium Channel Blockers; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Epilepsy; Flunarizine; Humans; Middle Aged

In a therapy-resistant epileptic population with partial complex seizures with or without secondary generalization, addition of flunarizine to existing therapy was accompanied by a significant reduction in complex partial and tonic-clonic seizures. This result did not appear to be due to serial effects or changes in the plasma levels of the co-medication. Side effects were rare. The serum flunarizine levels (13.8 ng/ml; range, 3-32.5 ng/ml) were lower than previously reported on a daily dose of 10 mg. This may reflect increased metabolism due to induction of liver enzymes by the co-medication. Given this finding, together with the low incidence of side effects, a further study is required to determine whether higher blood levels would give an improved degree and incidence of seizure reduction.

Topics: Adolescent; Adult; Cinnarizine; Drug Therapy, Combination; Epilepsy; Female; Flunarizine; Humans; Male; Middle Aged; Piperazines; Vasodilator Agents

The anticonvulsant activity of 1-bis(4-fluorophenyl)methyl-4-(3-phenyl-2-propenyl)-piperazine, flunarizine, was studied after intraperitoneal administration in DBA/2 mice (seizures induced by sound), intravenous administration in Papio papio (myoclonus induced by photic stimulation) and oral administration in Wistar rats (seizures induced by cefazolin). Protection against sound-induced seizures was observed after intraperitoneal administration of flunarizine (5-40 mg/kg). The ED50 for suppression of tonic, clonic and wild running phases of sound-induced seizures was 3.3, 9.8 and 17.5 mg/kg, respectively. This protective action was significantly reduced by pretreatment with aminophylline (50 mg/kg, i.p.). In photosensitive baboons flunarizine (0.5-1.0 mg/kg, i.v.) provided partial protection against myoclonic responses to stroboscopic stimulation. After flunarizine (2 mg/kg, i.v.) this protection lasted for more than 5 hr (and was complete at 2-3 hr). Cefazolin-induced seizures in rats were prevented by administration of flunarizine (20-40 mg/kg, orally). The ED50 for the suppression of tonic and clonic seizures evoked by subsequent intravenous administration of cefazolin was 25 mg/kg. The protective effects of flunarizine (40 mg/kg, orally) were maximal after 3-6 hr and were maintained for 16-24 hr. Behavioural effects of flunarizine included signs of sedation in both mice and rats. Tolerance to the antiepileptic effects of flunarizine was not seen after chronic treatment in rats. The role of purinergic receptors and of calcium entry blockade in the anticonvulsant action of flunarizine requires further study.

Topics: Acoustic Stimulation; Animals; Anticonvulsants; Cinnarizine; Epilepsies, Myoclonic; Epilepsy; Female; Flunarizine; Male; Mice; Mice, Inbred DBA; Papio; Photic Stimulation; Rats; Rats, Inbred Strains; Seizures

Topics: Animals; Animals, Suckling; Calcium Channel Blockers; Cinnarizine; Epilepsy; Flunarizine; Kindling, Neurologic; Male; Rats; Rats, Inbred Strains

The time relations of epileptic events have been studied in 3 sets of data: (I) counts of individual epileptiform discharges in twelve 48 h EEG recordings, (IIa) seizure calendars of 30 therapy-resistant outpatients participating in a drug trial, (IIb) seizure calendars of 10 mentally subnormal epileptic patients resident in a long-stay unit. The EEG data I were characterized most often by a Poisson distribution of intervals between discharges and the occurrence of marked periodicities, particularly at night. The periods of rhythmic nocturnal events ranged from 13 to 142 min and did not appear to correspond to the REM/non-REM cycle. In the seizure data IIa and b a Poisson distribution of intervals between events was found in half the patients. Periodicities occurred only in group IIa and did not correspond to weekly or monthly cycles. A stochastic process is considered to be the model which best fits these data.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Brain; Cinnarizine; Electroencephalography; Epilepsy; Female; Flunarizine; Humans; Male; Middle Aged; Placebos; Seizures; Telemetry; Time Factors