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

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

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*

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

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

Endoscopy is increasingly performed with the patient under conscious sedation in many countries. The majority of patients can be adequately and safely sedated during routine upper endoscopy and colonoscopy with a combination of a benzodiazepine and opioid. Midazolam is a water-soluble benzodiazepine that is characterized by a rapid onset of action and a shorter duration compared with that of the other drugs of the same class. The major side effect of midazolam is respiratory depression, which can be reversed by flumazenil, a benzodiazepine-specific antagonist. Propofol is a lipid-soluble agent that has the advantages of a more rapid onset of action and a shorter recovery time compared to that of midazolam. However, it should be used with caution since it can lead to hypotension and respiratory depression. Propofol can be safely and effectively administered by nonanesthesiology physicians and nurses provided that they have received adequate training. Two models have been proposed for the administration of propofol by endoscopists: nurse-administered propofol sedation (NAPS) and combination propofol (propofol plus other agents) sedation. In order to modify the pharmacological disadvantages of propofol, fospropofol sodium, a water-soluble prodrug of propofol, has recently been developed. In addition, new delivery systems have been devised: patient-controlled sedation and computer-assisted personalized sedation, in which the computer continuously monitors the patient's condition and adjusts the dose of propofol accordingly. Endoscopists must have a thorough understanding of the medications used for endoscopic sedation and they must acquire the skills necessary for the treatment of cardiopulmonary complications. Therefore, it is necessary to develop a practice guideline pertaining to endoscopic sedation and also training programs for physicians and nurses in Korea.
Benzodiazepines ; Colonoscopy ; Conscious Sedation ; Endoscopy ; Flumazenil ; Humans ; Hypotension ; Korea ; Midazolam ; Propofol ; Respiratory Insufficiency ; Sodium

Flumazenil, an imidazobenzodiazepine, is the first benzodiazepine antagonist and is being used to reverse the adverse pharmacological effects of benzodiazepine. There have been a few reports on the central nevous system side effects with its use. We report a patient with generalized ballism following administration of flumazenil. The mechanism through which flumazenil induced this symptom is unknown. It is conceivable that flumazenil may antagonize the GABA-benzodiazepine receptor complex and induce dopamine hypersensitivity, thus induce dyskinesic symptoms.
Diagnosis, Differential ; Dyskinesias/etiology* ; Female ; Flumazenil/adverse effects* ; GABA Modulators/adverse effects* ; Human ; Middle Aged

BACKGROUND: Midazolam relaxes airway smooth muscle. The aim of this study is to evaluate the influence of flumazenil or verapamil on the relaxation effects of midazolam in tracheal smooth muscle of guinea pig. METHODS: After isolating guinea-pig tracheal preparations, the maximal tracheal tones were induced by 2 10(-7) M carbachol. When tracheal tones stabilized, midazolam was added cumulatively (10(-6), 3 10(-6), 10(-5), 3 10(-5), 10(-4) M, n=14) with or without flumazenil (10(-6) M, n=15) and verapamil (10(-5) M, n=13) to obtain the concentration-relaxation curves, and then the ED50 and ED95 calculated. RESULTS: Midazolam decreased maximal tracheal smooth muscle tones in concentration-dependent manners. Pretreatment with flumazenil had no effect on the midazolam-induced relaxation. Verapamil enhanced the relaxation effect of midazolam. CONCLUSIONS: Midazolam relaxes airway smooth muscle and has synergistic effect with calcium channel blocker, verapamil.
Animals ; Calcium Channels ; Carbachol ; Flumazenil* ; Guinea Pigs ; Midazolam* ; Muscle, Smooth* ; Relaxation* ; Verapamil*

The effects of flumazenil, a benzodiazepine antagonist were evaluated in a clinical study in which midazolam (0.1 mg/kg) was used as a sedative agent during the spinal anesthesia. Sixty patient were divided into two groups as group F (n=30) and group S (n=30). Flumazenil 0.3 mg (3 mL) in group F and saline 3 mL in group S were administered at the end of surgery. Blood pressure, pulse rate, respiratory rate and oxygen saturation (SaO2) were checked just before and at, 5, 15, 30, 60 and 120 minutes after the administration of flumazenil or saline. Also we evaluated the level of conciousness and orientation in time and space. The results were as follows; 1) Changes in blood pressure, pulse rate and respiratory rate were not different between two groups, exeept SaO2 was which increased significantly in the flumazenil group. 2) The flumazenil group revealed improved level of consciousness and orientation in time and space which began 5 minutes after flumazenil and was maintained 30 minutes thereafter. 3) We could not observe the any side effects of flumazenil.
Anesthesia, Spinal* ; Benzodiazepines ; Blood Pressure ; Consciousness ; Flumazenil* ; Heart Rate ; Humans ; Midazolam* ; Oxygen ; Respiratory Rate