flunarizine and Substance-Related-Disorders

The effect of acute and chronic treatments of the calcium-channel blockers, isradipine, diltiazem and flunarizine in protecting against lorazepam dependence has been demonstrated in mice. Dependence was induced by twice-daily administration of lorazepam (1 mg kg-1) for 10 days, doubling the dose during the next 10 days. Withdrawal symptoms and changes in the noradrenaline, dopamine and 5-hydroxytryptamine content of different regions of the brain were observed after either 24-h withdrawal or flumazenil administration. Isradipine inhibited lorazepam withdrawal symptoms, the effect being accompanied in the 24-h withdrawal group by significant decreases in the noradrenaline and dopamine content of the thalamus and hypothalamus and in the noradrenaline content of the mid-brain. In the flumazenil-treated group isradipine produced significant decreases in mid-brain noradrenaline and dopamine levels and in the dopamine content of the thalamus and hypothalamus. Diltiazem did not, on the other hand, afford significant protection against lorazepam withdrawal symptoms and did not induce any significant change in the neurotransmitters studied. Flunarizine significantly inhibited lorazepam withdrawal symptoms, an effect accompanied by significant reduction in noradrenaline and dopamine levels in the thalamus and hypothalamus. Dopamine was also significantly reduced in the cerebral cortex. Similar effects were produced in the flumazenil-treated group, and the noradrenaline content was reduced in the medulla, pons and cerebellum. It was concluded that isradipine and flunarizine might be of value in ameliorating lorazepam withdrawal symptoms.

Topics: Animals; Brain Chemistry; Calcium Channel Blockers; Diltiazem; Dopamine; Flunarizine; Isradipine; Lorazepam; Male; Mice; Norepinephrine; Serotonin; Substance Withdrawal Syndrome; Substance-Related Disorders

To analyse the results of out-patient treatment with diminishing doses of oral dihydroergotamine for patients with chronic migraine resulting from ergotics abuse.. A prospective and descriptive intervention study.. County hospital. Neurology out-patient clinic.. All the patients with chronic migraine as a side-effect of abuse of ergotic preparations who were referred to neurology out-patients over 18 months.. 1) Patients were told verbally of the causes of their migraine; 2) suppression of the ergotics, using diminishing doses of dihydroergotamine (Dihydergot gotas); 3) Prophylactic treatment with flunarizine (Sibelium); 4) Symptomatic treatment with sodic naproxen (Antalgin 550); 5) monthly and three-monthly check-up.. Over 18 months 25 patients with migraines due to ergotic abuse (6.7% of total migraines) were included. 4 were men; 21 women. Their average age was 43 (SD: 13). At one month the response was excellent in 19 patients (76%), good in 3 (12%) and bad in 3 (12%). At three months, the response was excellent in 17 patients (68%), good in 4 (16%), bad in 2 (8%) and 2 did not attend for the check-up (8%).. 1) Out-patient treatment with diminishing doses of oral dihydroergotamine is effective in treating chronic migraine due to ergotics abuse. 2) The general practitioner should intervene in the identification and prevention of ergotics abuse.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Dihydroergotamine; Ergot Alkaloids; Female; Flunarizine; Headache; Humans; Male; Middle Aged; Naproxen; Prospective Studies; Substance-Related Disorders; Time Factors; Vasodilator Agents

Topics: Affect; Depressive Disorder; Flunarizine; Humans; Male; Middle Aged; Migraine Disorders; Problem Solving; Substance-Related Disorders

The effects of Ca2+ channel blockers on the development of physical dependence on diazepam were examined in mice. Co-administration of flunarizine (T-type Ca2+ channel sensitive blocker), but not of either nifedipine or diltiazem (L-type Ca2+ channel sensitive blockers), with diazepam significantly suppressed the hypersensitivity to FG 7142 following chronic treatment with diazepam. The hypersensitivity to FG 7142 may reflect benzodiazepine withdrawal convulsions. These results suggest that flunarizine, but not nifedipine or diltiazem, may suppress the development of physical dependence on diazepam, and that T-type Ca2+ channels in the brain, rather than L-type Ca2+ channels, may be involved in the development of physical dependence on diazepam.

Topics: Animals; Brain; Calcium Channel Blockers; Carbolines; Diazepam; Diltiazem; Drug Interactions; Flunarizine; Male; Mice; Mice, Inbred ICR; Nifedipine; Receptors, GABA-A; Seizures; Substance-Related Disorders

The effects of flunarizine and diltiazem both on development of physical dependence on barbital and on barbital withdrawal signs in rats were examined using the drug-admixed food (DAF) method. Rats were chronically treated with barbital or barbital in combination with flunarizine (fixed at 1.5 mg/g of food) or diltiazem (fixed at 0.75 mg/g of food)-admixed food on the schedule of gradually increasing doses of barbital. Motor incoordination during the treatment was potentiated by coadministration of flunarizine, but not by coadministration of diltiazem. After the termination of drug treatment, the body weight loss and withdrawal scores were significantly suppressed in the group coadministered flunarizine, but not in that coadministered diltiazem. There were no significant differences in plasma barbital levels after the withdrawal between groups. In the substitution test, flunarizine (20 and 40 mg/kg, IP) significantly suppressed the body weight loss and withdrawal scores after the withdrawal, but diltiazem (20 mg/kg, IP) did not. These results indicated that flunarizine suppressed both the development of physical dependence on barbital and barbital withdrawal signs, mainly according to the suppression of convulsions, but not diltiazem, which is known to poorly penetrate into the brain. Therefore, the present findings suggest that central calcium channels may be involved in both the development of physical dependence on barbital and the appearance of barbital withdrawal signs.

Topics: Animals; Barbital; Calcium Channel Blockers; Calcium Channels; Diltiazem; Flunarizine; Male; Postural Balance; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome; Substance-Related Disorders; Weight Loss