Benzodiazepines antagonists

Brogden RN, Goa KL Flumazenil a preliminary review of its benzodiazepine antagonist properties, intrinsic activity and therapeutic use. Drugs 35 448 67, 1988... 

Darragh A, Lambe R, Kenny M, et al Tolerance of healrhy volunteers to intravenous administration of the benzodiazepine antagonist Ro 15-1788. EurJ Clin Pharmacol 24 569-370, 1983... 

Evidence for the false transmitter theory as the cause of encephalopathy is demonstrated by the fact that administration of flumazenil (a benzodiazepine antagonist) has resulted in functional improvement. Unfortunately, long-term benefit has not been shown, and since flumazenil can only be administered par-enterally, it is not an appropriate choice for long-term therapy. 

Bishop KI and Curran HY (1995). Psychopharmacological analysis of implicit and explicit memory A study with lorazepam and the benzodiazepine antagonist flumazenil. Psychopharmacology, 121, 267-278. 

Baraldi M, Zeneroli ML, Ventura E, Penne A, Pinelli G, Ricci P, Santi M Supersensitivity of benzodiazepine receptor in hepatic encephalopathy due to fulminant hepatic failure in the rat Reversal by a benzodiazepine antagonist. Clin Sci 1984 67 167-175. 

Sedative and anxioiytic effects A number of flavonoids have been shown to bind to benzodiazepine receptors and have anxiolytic effects (Medina et al. 1997). The anxiolytic effects of chrysin were examined in mice (Wolfman et al. 1994). Chrysin (1 mg/kg IP) reduces behavioral measures of anxiety (elevated-plus maze) in a manner similar to diazepam (0.3-0.6 mg/kg), which was reversed by pretreatment with a benzodiazepine antagonist, Ro 15-1788. The anxiolytic effect is not likely due to sedation because there is no concurrent reduction in motor activity at the doses used. Unlike diazepam, chrysin does not produce muscle relaxation at higher doses. 

Antiseizure effects One study examined antiseizure effects of chrysin on chemically induced (pentylenetetrazol) seizures in mice (Medina et al. 1997). Peripheral (IP) administration produced inconsistent effects, but central (intracerebroventricular) injection (40 pg) had a significant anticonvulsant effect. Further, this effect was abolished by prior injection of the benzodiazepine antagonist, Ro 15-1788 (3 mg/kg IP). 

File SE, Lister RG, Nutt DJ. (1982). The anxiogenic action of benzodiazepine antagonists. Neuropharmacology. 21(10) 1033-37. 

Flumazenil is a benzodiazepine antagonist that is used in anaesthesia for the reversal of central sedative effects of benzodiazepines. It should not be administered rapidly so as to avoid patient wakening too rapidly, which can lead to agitation, anxiety, fear and convulsions, particularly in high-risk patients, e.g. those with a history of epilepsy or head injury. 

With any hypnotic, the risk of suicidal overdosage cannot be ignored. Since benzodiazepine intoxication may become life-threatening only when other central nervous depressants (ethanol) are taken simultaneously and can, moreover, be treated with specific benzodiazepine antagonists, the benzodiazepines should be given preference as sleep remedies over the all but obsolete barbiturates. 

Benzodiazepine antagonists, such as flumazenil, possess affinity for benzodiazepine receptors, but they lack intrinsic activity. Flumazenil is an effective antidote in the treatment of benzodiazepine overdosage or can be used postoperatively to arouse patients sedated with a benzodiazepine. 

Flumazenil is a benzodiazepine antagonist and is used to accelerate the recovery from the sedative actions of benzodiazepines in overdosed patients or af-... 

Flumazenil Romazicon) is a benzodiazepine antagonist that specifically reverses the respiratory depression and hypnosis produced by the benzodiazepine receptor agonists. Its block of the amnesic effect of the agonists is less reliable. Flumazenil is particularly useful when an overdose of benzodiazepines has occurred. It is also employed when a benzodiazepine has been used to produce conscious sedation and rapid recovery of psychomotor competency is desirable. To avoid resedation, flumazenil may require administration by intravenous infusion. 

HT2, and receptors and possesses very little extrapyramidal toxicity but significant sedative and autonomic side effects. Flumazenil is a benzodiazepine antagonist, and carbamazepine is an anticonvulsant neither possesses significant antipsychotic properties. 

The promising anxiolytic-antipanic preclinical profile of bretazenil, an imidazobenzodiazepine congener of the benzodiazepine antagonist flumazenil (Katschnig et al. 1991), also has not been confirmed in large-scale clinical testing. 

In an emergency setting, the benzodiazepine antagonist fluma-zenil may be given intravenously to reverse the effects of a potential overdose of a benzodiazepine. Caution in use of flumazenil in a mixed overdose with tricychc antidepressants (TCAs) is warranted, however. Its use may precipitate TCA-induced arrhythmias and seizures that were suppressed by benzodiazepines. 

The C02 inhalation challenge and sodium lactate infusion challenge paradigms show high specificity for panic disorder but less sensitivity than the cholecystokinin (CCA) or methyl-chlorophenylpiperazine (niCPP) challenge tests, which are also able to provoke panic symptoms and anxiety in health volunteers. Flumazenil a benzodiazepine antagonist can provoke panic attacks in some panic disorder patients but with lower sensitivity than sodium lactate infusion, C02 or CCK. 

An analogue of these fused benzodiazepines in which the benzene ring at the 5 position is omitted shows benzodiazepine antagonist activity in both in vitro binding... 

Dorow R, Berenberg D, Duka T, et al. Amnestic effects of lormetazepam and their reversal by the benzodiazepine antagonist Ro 15-1788. Psychopharmacology 1987 93 507-514. 

Flumazenil is a competitive benzodiazepine antagonist with a half-life of approximately 1 hour. It is available only as an intravenous injection. Since its half-life is shorter than the drugs which it is used to antagonise, its beneficial effects are temporary. It is perhaps best used as a means of establishing a diagnosis before instituting appropriate supportive therapy. Flumazenil has been reported as inducing withdrawal symptoms in some habitual benzodiazepine users. 

The benzodiazepine antagonist flumazenil can be used to accelerate recovery when excessive doses of intravenous benzodiazepines are administered (especially in elderly patients). However, reversal of benzodiazepine-induced respiratory depression is less predictable. The short duration of action (< 90 minutes) of flumazenil may necessitate multiple doses to prevent recurrence of the CNS depressant effects of the longer-acting benzodiazepines (eg, lorazepam, diazepam). 

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