Pharmacological aspects of withdrawal from certain benzodiazepines.
The aim of the study was to investigate, if the occurrence of benzodiazepine withdrawal syndrome is connected with benzodiazepine receptors, their down-regulation as well as with the number of drug applications. The results showed that symptoms of withdrawal measured by the anxiolytic and sedative effects occurred after chronic treatment with alprazolam for 14-21 days and after chlordiazepoxide daily administration for 35 days, and in both cases, after 48-hour abstinence period. In the same experimental design Ro 15-1788 administered at a dose of 10 mg/kg i.p. 25 min prior to examination prevented the development of the anxiogenic and locomotor stimulating withdrawal response in these rats. The symptoms of withdrawal measured by the sedative and anxiolytic effects were accompanied by a down-regulation of benzodiazepine receptors. It can be assumed that the process of withdrawal from benzodiazepines is related to benzodiazepine receptors, and that the number of drug applications plays an important role.
Nowakowska
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Department of Pharmacology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
Chodera
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Kus
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D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001569:Benzodiazepines / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D000931:Antidotes; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil