Flumazenil, an imidazobenzodiazepine derivative, is an antagonist of the GABA/benzodiazepines receptor complex that might play a role in the treatment of hepatic encephalopathy[3]. Flumazenil can antagonize the hypnotic and sedative effects of benzodiazepines at gamma-amino butyric acid receptors. Flumazenil could be considered in cases in which quick recovery is required and should be administered intravenously in small, incremental doses[4]. Intravenous antagonist doses of 0.2 mg followed by 0.1 mg/min to a total dose of 1 mg have produced significant results in reversing benzodiazepine sedation. As much as 5 mg of flumazenil have been necessary when treating benzodiazepine or mixed-agent intoxications. Flumazenil is well tolerated locally as well as systemically[5]. Because flumazenil appears to be specific in its antagonism of benzodiazepine-induced respiratory and CNS depression, it could be used empirically to confirm or exclude a role of benzodiazepines in the generation of mental status changes in the setting of overdose or coma of unknown origin[6].
Flumazenil/氟马西尼 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human colonic organoids
1 µM
1-hour pretreatment
Flumazenil increased the number and size of human organoids post 5-FU/irradiation treatment.
J Exp Med. 2022 Dec 5;219(12):e20220541.
Human colonic organoids
1 µM
48 hours
Flumazenil alleviated 5-FU or irradiation-induced toxicity in human colonic organoids, increasing the number and size of organoids.
J Exp Med. 2022 Dec 5;219(12):e20220541.
HEK293T cells
3 µM
Flumazenil inhibited isoflurane-mediated GABA current enhancement and exhibited weak agonist activity at 1 μM
Anesthesiology. 2016 Jul;125(1):147-58.
Flumazenil/氟马西尼 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
Isoflurane anesthesia model
Intravenous injection
0.4 mg/kg
Single administration
Flumazenil hastened behavioral and neurophysiological markers of emergence from isoflurane anesthesia and mitigated the increase in post-anesthesia sleep time
Anesthesiology. 2016 Jul;125(1):147-58.
Mice
5-FU or irradiation-induced intestinal injury model
Intraperitoneal injection
1 mg/kg
6 days (5-FU) or single dose (irradiation)
Flumazenil significantly alleviated 5-FU or irradiation-induced intestinal injury in mice, increasing the number of TACs, proliferative capacity, and OLFM4+ ISCs, and reducing DNA double-strand breaks.
J Exp Med. 2022 Dec 5;219(12):e20220541.
Rhesus monkey
Rhesus monkey model
Intravenous injection
1 mg/kg
Single dose, duration 90 minutes
To evaluate the in vivo pharmacokinetics of [18F]AH114726 and [18F]GEH120348 in non-human primates and directly compare them with [11C]FMZ. Results showed that [18F]AH114726 had pharmacokinetics most similar to [11C]FMZ, while [18F]GEH120348 showed higher initial brain uptake but slower clearance.
Molecules. 2020 Nov 30;25(23):5647
Rhesus monkey
Rhesus monkey model
Intravenous injection
1 mg/kg
Single dose, duration 90 minutes
To evaluate the in vivo pharmacokinetics of [18F]AH114726 and [18F]GEH120348 in non-human primates and directly compare them with [11C]FMZ. Results showed that [18F]AH114726 had pharmacokinetics most similar to [11C]FMZ, while [18F]GEH120348 showed higher initial brain uptake but slower clearance.
Nucl Med Biol. 2013 Oct;40(7):901-5
Planarians (Dugesia dorotocephala)
Drug withdrawal model
Immersion
10 µM
1-hour exposure, 5-minute test
Flumazenil significantly antagonized the withdrawal effects induced by three benzodiazepine receptor agonists (midazolam, clorazepate, and zolpidem), as evidenced by a significant prevention of the reduction in pLMV.
Eur J Pharmacol. 2007 Jun 14;564(1-3):88-93
Mice
Anxiety and anticonvulsant models
Intraperitoneal injection
2 mg/kg
Single dose, administered 15 minutes before NPT
To evaluate the antagonistic effect of Flumazenil on the anxiolytic-like and anticonvulsant effects of NPT. Results showed that Flumazenil significantly reversed the anxiolytic-like and anticonvulsant effects of NPT.
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