No abstract available.
Electroencephalography ; Flumazenil* ; Status Epilepticus*

We investigated the usefulness of the method of producing sedation with midazolam and reversing with antagonist flumazenil in upper gastrointestinal endoscopy. Twenty-five adult outpatients underwent diagnostic upper gastrointestinal endoscopy 3 min after having an intravenous injection of 5 mg of midazolam for sedation, and received 0.25 mg of flumazenil intravenously 5 min after the removal of the endoscope. Blood pressure, heart rate, and percutaneous arterial oxygen saturation (SpO2) were measured, recorded, and compared at nine points : 1 min before midazolam injection, 2 min after midazolam injection, 1, 3, and 5 min after the insertion of the endoscope, 1 and 3 min after the removal of the endoscope, 1 min after flumazenil injection, and their awakening time at which they are easily able to respond to verbal commands. Fifteen minntes after their awakening, we asked those patients about their memory during the endoscopy and evaluated their pain with the Visual Analogue Scale (VAS). A significant decrease in systolic blood pressure was noted 2 min after midazolam injection. But the systolic blood pressure measured 1 min after the insertion of the endoscope significantly increased when compared with the level 2 min after midazolam injection. Then it gradually started decreasing. Although the systolic blood pressures 1 min after flumazenil injection and at their awakening time increased slightly, the levels were significantly lower than those 1 min before midazolam injection. The heart rate increased to the maximum 1 min after the insertion of the endoscope. Then it gradually started decreasing. The heart rates 1 min after flumazenil injection and at their awakening time decreased significantly when compared with those 1 min after the insertion of the endoscope. SpO2 significantly decreased from 97.6±1.6% 1 min before midazolam injection to 95.7±2.5% 2 min after midazolam injection and remained depressing around 95% during the endoscopy. However, SpO2 recovered 96.6±2.0% at their awakening time. Two patients had a vague memory but all the rest had no memory recollection at all of what happened during the examination. VAS was 20 mm for one patient and 0 mm for another patient. We showed the clinical usefulness of the method of antagonizing with flumazenil after upper gastrointestinal endoscopy performed on patients given an i.v. injection of midazolam, because this method might provide a minimal circulatory change due to some protection against hemodynamics stress in response to manipulation of the endoscope, anterograde amnesia, and disappearance of pain. However, we should take care of respiratory depression of the patient during endoscopy.
Minute of time ; Midazolam ; Injections ; Flumazenil ; Awake

PURPOSE: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F- 18]fluoro)flumazenil, a new fluorine-18 (t1/2=110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. MATERIALS AND METHODS: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at 85 degree C in the hot cell for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection. RESULTS: The total chemical yield of tosylated flumazenil derivative was ~40%. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were 2.5+/-0.37, 2.2+/-0.26, 2.1+/-0.11 and blood activities were 3.7+/-0.43, 3.3+/-0.07, 3.3+/-0.09%ID/g, respectively. CONCLUSION: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.
Animals ; Benzodiazepines* ; Brain ; Ethanol ; Flumazenil* ; Injections, Intravenous ; Mice ; Receptors, GABA-A*

PURPOSE: Flutamide (4-nitro-3-t-trifluoromethyl-isobutyranilide) is an androgen-receptor antagonist with typical antiandrogenic effect, used to treat androgen-dependent disorders such as prostate cancer. However, some reports noted that flutamide has direct effects to neuronal cells. It has been shown to retard the development of electrical kindling in rats. METHODS: We used the chemoconvulsant 4-aminopyridine (4-AP) and picrotoxin (PTX) in the in vitro hippocampal slice model to determine of flutamide for the suppression of epileptiform discharges. Extracellular field potential recordings were obtained from the CA3 pyramidal layer of hippocampus. RESULTS: The concentration of 30 and 100 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 57.8% and 66.8% each compared with the 4-AP only slices. In 100 micrometer PTX, 10 and 30 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 56.6% and 82.5% each. Intermixed with flumazenil, the anticonvulsant effect of flutamide was decreased. CONCLUSIONS: Flutamide suppressed epileptiform discharges induced by 4-AP and PTX in vitro seizure model. It suggests that flutamide influence to anti-epileptic activity by benzodiazepine site of the GABAA receptor.
4-Aminopyridine ; Benzodiazepines ; Flumazenil ; Flutamide ; Neurons ; Picrotoxin ; Prostatic Neoplasms ; Seizures

The effects of lorazepam on cerebral function, metabolism, and hemodynamics were studied in eight dogs receiving a general anesthesia with isoflurane(0.5 vo1%)-50% nitrous oxide-oxy-gen. The effects of benzodiazepine antaronist, flumazenil, were also examined. Lorazepam(0.5 mg/kg) administration did decrease mean arterial pressure(MAP) and herat rate(HR). It did significantly decrease cerebral blood flow(CBF)(measured by posterior sagittal sinus outflow method) by 25% of control value(68+/-l3 vs. 51+/-12ml/100gm/min, meanSD) and cereberal metabolic rate for oxygen(CMRO ) by 17% (3.96+/-1.04 vs. 3.30+/-0.92ml/l00gm/min, mean+/-SD). Electroencephalogram(EEG) converted to high amplitude, predominantly theta and delta activity. Intracranial pressure(ICP) increased markedly. Following flumazenil(0.06 mg/kg) administration, HR recovered completely to control level but MAP increased only at 5 min. compared to pre-flumazenil value and returned to pre-flumazenil level. CBF recovered to control level for 15 min. and deereased after 30 min. compared to control level but higher than pre-flumazenil level about 9-15%. CMRO recovered completely to control leveL EEG changed to an awake pattern after fluamzenil administration. It is concluded that lorarepam decreased cerebral function and metabolism and depressed hemodynamic fuction. Benzodiazepine antag- onist, flumazenil, was effective in reversing cerebral and hemodynamic effects, may be in dose related manner.
Anesthesia, General ; Animals ; Benzodiazepines ; Dogs* ; Electroencephalography ; Flumazenil* ; Hemodynamics ; Lorazepam* ; Metabolism

Prolonged oversedation occurs frequently in postoperative care units, and sometimes delays transfer to normal units. Flumazenil is a known reversal drug for benzodiazepines, and is used to reverse the oversedation caused by benzodiazepines. However, we found that flumazenil was effective in a case of sevoflurane induced oversedation. A prolonged oversedation of 90 minutes occurred after sevoflurane anesthesia without benzodiazepine at a postoperative care unit. Immediately after an intravenous injection of flumazenil, the patient fully awoke and was oriented.
Anesthesia* ; Benzodiazepines ; Flumazenil* ; Humans ; Injections, Intravenous ; Postoperative Care

Isoliquiritigenin (ILTG) is a chalcone compound and shows various pharmacological properties, including antioxidant and anti-inflammatory activities. In recent study, we have reported a novel role of ILTG in sleep through a positive allosteric modulation of gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptors. However, the effect of ILTG in GABA(A)R-mediated synaptic response in brain has not been tested yet. Here we report that ILTG significantly prolonged the decay of spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by GABA(A)R in mouse hippocampal CA1 pyramidal neurons without affecting amplitude and frequency of sIPSCs. This enhancement was fully inhibited by flumazenil (FLU), a specific GABA(A)-BZD receptor antagonist. These results suggest a potential role of ILTG as a modulator of GABAergic synaptic transmission.
Animals ; Brain ; Chalcone* ; Flumazenil ; gamma-Aminobutyric Acid ; Inhibitory Postsynaptic Potentials ; Mice ; Neurons ; Synaptic Transmission

BACKGROUND/AIMS: Midazolam is utilized as a premedication for uppoer gastrointestinal endoscopy. Midazolam has a more rapid onset of reaction than that of diazepam and its duration is shorter. But the Consciousness of premedicated patients has not been regained sooner. The Purpose of this study was to examine the effectiveness of flumazenil against midazolam as premedication for upper gastrointesinal endoscopy. METHODS: Sixty patients underwent upper gastrointestinal endoscopy. These patients were divided to three groups: Group I included twenty patients without premedication; Group II Included twenty patients with premedication of midazolam and then were not given an antisedative agent excluign of normal saline; and Group III included the others with midazolam and flumazenil as an antisedative agent. RESULTS: There was no change in vital signs after midazolam and flumazenil as an antisedative agent. RESULTS: There was no change in vital signs after midazolam injection, compared with presedation value. Modified Steward Coma Scale showed a significant increase after flumazenil injection as an antagonist of midazolam. The assessment of the endoscopist and the comfort of patients were satisfactory. When the 40 patients were asked about their willingness to undergo the same procedure in the future, thirty-four patients responded favorably. CONCLUSION: Midazolam was safe and effective for sedation for upper gastrointestinal endoscopy. There was rapid regaining of consciousness with flumazenil indection after midazolam, so the use of flumazenil against midazolam injection also appeared to be effective.
Coma ; Consciousness ; Diazepam ; Endoscopy ; Endoscopy, Gastrointestinal* ; Flumazenil* ; Humans ; Midazolam* ; Premedication* ; Vital Signs

BACKGROUND/AIMS: Midazolam is widely used as a form of conscious sedation during endoscopy because of its rapid onset and safety. However, its relatively long half-life and paradoxical reactions are still a concern for doctors and patients. Flumazenil is a competitive benzodiazepine antagonist that acts to reverse the sedative and hypnotic effects of midazolam but its role and adequate dose have not been fully documented. This study evaluated the effect of a fixed dose of flumazenil on the recovery from sedative endoscopy by midazolam. METHODS: First study: 100 patients who received 0.05 mg/kg midazolam for conscious sedation were randomized into two groups: intravenous 0.25 mg flumazenil and a placebo. All patients were assessed using OAA/S (Observers Assessment of Alertness/Sedation Scale) scale (responsiveness, speech, facial expression and ptosis of eyelid) before the endoscopy, immediately after the procedure and every 5 minutes thereafter. The recovery time was defined as the time at which the OAA/S scale reached the pre-endoscopy level. Second study: In 40 patients, the OAA/S scale was assessed only after full recovery without any exogenous stimuli. The total dose of midazolam and the procedure time were assessed. RESULTS: The flumazenil group demonstrated a significantly shorter recovery time than the placebo group (p<0.0001). These results were not affected by age, gender, total midazolam dose and procedure time. There was a larger difference in the recovery time between the two groups in the second study than in the first. CONCLUSIONS: A fixed low dose flumazenil significantly reduced the recovery time after sedative endoscopy by midazolam. Flumazenil will be helpful for the early return to daily activities and for preventing post sedative complication.
Benzodiazepines ; Conscious Sedation ; Endoscopy* ; Facial Expression ; Flumazenil* ; Half-Life ; Humans ; Hypnotics and Sedatives ; Midazolam*

BACKGROUND/AIMS: Midazolam is widely used as a form of conscious sedation during endoscopy because of its rapid onset and safety. However, its relatively long half-life and paradoxical reactions are still a concern for doctors and patients. Flumazenil is a competitive benzodiazepine antagonist that acts to reverse the sedative and hypnotic effects of midazolam but its role and adequate dose have not been fully documented. This study evaluated the effect of a fixed dose of flumazenil on the recovery from sedative endoscopy by midazolam. METHODS: First study: 100 patients who received 0.05 mg/kg midazolam for conscious sedation were randomized into two groups: intravenous 0.25 mg flumazenil and a placebo. All patients were assessed using OAA/S (Observers Assessment of Alertness/Sedation Scale) scale (responsiveness, speech, facial expression and ptosis of eyelid) before the endoscopy, immediately after the procedure and every 5 minutes thereafter. The recovery time was defined as the time at which the OAA/S scale reached the pre-endoscopy level. Second study: In 40 patients, the OAA/S scale was assessed only after full recovery without any exogenous stimuli. The total dose of midazolam and the procedure time were assessed. RESULTS: The flumazenil group demonstrated a significantly shorter recovery time than the placebo group (p<0.0001). These results were not affected by age, gender, total midazolam dose and procedure time. There was a larger difference in the recovery time between the two groups in the second study than in the first. CONCLUSIONS: A fixed low dose flumazenil significantly reduced the recovery time after sedative endoscopy by midazolam. Flumazenil will be helpful for the early return to daily activities and for preventing post sedative complication.
Benzodiazepines ; Conscious Sedation ; Endoscopy* ; Facial Expression ; Flumazenil* ; Half-Life ; Humans ; Hypnotics and Sedatives ; Midazolam*