Benzodiazepine antagonists flumazenil

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. 

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. 

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). 

The most widely studied aspect of cognition with respect to benzodiazepines is memory.12 163 One of the most reliable effects of benzodiazepines is to impair recall of information presented after drug administration (anterograde amnesia). In contrast, information presented before administration of benzodiazepines is not affected. The memory decrement produced by benzodiazepines is a function of task difficulty, such that little or no impairment is observed for immediate recall of a few items, whereas more complex or delayed memory tests reveal profound impairment.12 The benzodiazepine antagonist flumazenil has been used to block the sedative effects of benzodiazepines, but the amnestic effect was not affected, suggesting that benzodiazepine-induced amnesia is independent of sedation.122,164 It has also been demonstrated that some benzodiazepines selec-... 

Curran, H.V. and Birch, B., Differentiating the sedative, psychomotor and amnesic effects of benzodiazepines a study with midazolam and the benzodiazepine antagonist, flumazenil, Psychopharmacology, 103, 519, 1991. 

Wesensten NJ, Balkin TJ, Belenky G. Is the benzodiazepine antagonist flumazenil intrinsically alerting (abstr) Sleep Res 1996 25 74. 

The relationship between drug concentration and response also can be altered in patients with advanced liver disease. Of greatest concern is the fact that customary doses of sedatives may precipitate the disorientation and coma that are characteristic of portal-systemic or hepatic encephalopathy. Experimental hepatic encephalopathy is associated with increased y-aminobutyric acid-mediated inhibitory neurotransmission, and there has been some success in using the benzodiazepine antagonist flumazenil to reverse this syndrome (50). This provides a theoretical basis for the finding that brain hypersensitivity, as well as impaired drug elimination, is responsible for the exaggerated sedative response to diazepam that is exhibited by some patients with chronic liver disease (51). Bakti et al. (52) conducted a particularly well-controlled... 

Ferenci P, Grimm G, Meryn S, Gangl A. Successful long-term treatment of portal-systemic encephalopathy by the benzodiazepine antagonist flumazenil. Gastroenterology 1989 96 240-3. 

Benzodiazepine antagonist flumazenil is a competitive antagonist at benzodiazepine receptors and it may have some agonist actions, i.e. it is a partial agonist. Clinical uses include reversal of benzodiazepine sedation after endoscopies, dentistry and in intensive care. Heavily sedated patients become alert within 5 minutes. The t) of 1 h is much shorter than that of most benzodiazepines (see Table 19.8), so that repeated i.v. administration may be needed. Thus the recovery period needs supervision lest sedation recurs if used in day surgery it is im-... 

In foals that have been overdosed, the benzodiazepine antagonist flumazenil may be of help (see Ch. 15). 

There may also be rare occasions when the benzodiazepine antagonist flumazenil could be used in horses (see Ch. 9). 

The benzodiazepine antagonist flumazenil is available for the complete reversal of benzodiazepine effects however, because of the mild degree of effects, the relative safety of benzodiazepines and the potential to produce excitability, the reversal of benzodiazepines is rarely indicated. Flumazenil is contraindicated in head trauma because it may elevate intracranial pressure (ICP). 

Meier R, Gyr K. Treatment of hepatic encephalopathy (HE) with the benzodiazepine antagonist flumazenil a pilot study. Eur J Anaesthesiol Suppl 1988 2 139-46. 

---