3-Carene, a bicyclic monoterpene, is one of the major components of the pine tree essential oils. It has been reported that, in addition to its known properties as a phytoncide, 3-carene has anti-inflammatory, antimicrobial, and anxiolytic effects. We have previously demonstrated that α-pinene, the major component of pine tree, has a hypnotic effect through GABA(A)-benzodiazepine (BZD) receptors. However, a hypnotic effect of 3-carene has not been studied yet. Here, we report that oral administration of 3-carene increases the sleep duration and reduces sleep latency in pentobarbital-induced sleep test. 3-Carene potentiates the GABA(A) receptor-mediated synaptic responses by prolonging the decay time constant of inhibitory synaptic responses. These enhancing effects of 3-carene are reproduced by zolpidem, a modulator for GABA(A)-BZD receptor, and fully inhibited by flumazenil, an antagonist for GABA(A)-BZD receptor. The molecular docking of 3-carene to the BZD site of GABA(A) protein structure, suggests that 3-carene binds to the BZD site of α1 and ϒ2 subunits of GABA(A)-BZD receptor. These results indicate that, similar to α-pinene, 3-carene shows a sleep-enhancing effect by acting as a positive modulator for GABA(A)-BZD receptor.
Administration, Oral ; Anti-Anxiety Agents ; Flumazenil ; Hypnotics and Sedatives ; Oils, Volatile ; Pinus

BACKGROUND: Intravenous administration of midazolam is widely used as a premedication for esophagogastroduonenoscopy. However, there are individual differences in midazolam doses for premedication and controversies for starting point of esophagogastroduonenoscopy after midazolam injection. There are also controversies for flumazenil injection time after esophagogastroduonenoscopy. The aims of this study were to determine the proper doses of midazolam for esophagogastroduonenoscopy and factors which affect midazolam doses. Also we evaluated the proper timing of flumazenil injection to increase patient's satisfaction according to sedation status. METHODS: 126 patients who were supposed to be taken diagnostic esophagogastroduonenoscopic exam were enrolled in this study. We evaluated the difference of patient's age, sex, alcohol consumption, sedation score, cooperation score, and satisfaction score according to midazolam doses. The relation between midazolam doses and agitation score, insomnia score, and somatic preoccupation score were checked. We evaluated the relation between midazolam doses and age, sex, alcohol consumption, amnesia, sedation, cooperation and satisfaction. RESULTS: There were no relationship between age, sex and midazolam doses. Alcoholics needed larger amount of midazolam than non-alcoholics. No differences in satisfaction were observed according to sedation status. There were significant relationship between midazolam doses and sedation score but not with satisfaction, cooperation, amnesia, agitation, insomnia and somatic preoccupation score. Patients who were injected flumazenil 20 minutes after esophagogastroduonenoscopy were more satisfied than patients who were injected flumazenil immediately after esophagogastroduonenoscopy. CONCLUSION: Minimal doses of midazolam that could induce mild sedation was enough and safe. Flumazenil injection 20 minutes after esophagogastroduonenoscopy was more efficacious than immediate injection.
Administration, Intravenous ; Alcohol Drinking ; Alcoholics ; Amnesia ; Conscious Sedation ; Dihydroergotamine ; Endoscopy, Digestive System* ; Flumazenil* ; Humans ; Individuality ; Midazolam* ; Premedication ; Sleep Initiation and Maintenance Disorders

The effects of midazolam and diazepam which were used as an induction agent of general anesthesia were evaluated. And flumazenil which is a potent competitive inhibitor of the specific binding of benzodiazepines at the receptor level was evaluated too. Sixty patients were divided into three groups as follows: Group I (n=20); Midazolam (average 0.24 mgkg-1) was administered as an induction agent and flumazenil (average 0.24 mgkg-1) was administered in recovery room Group II (n=20); Diazepam (average 0.35 mgkg-1) was administered as an induction agent and flumaxenil (average 0.25 mgkg-1) was administered in recovery room Group III (n=20); Midazolam (average 0.24 mgkg-1) was administered as an induction agent and normal saline was administered in recovery room instead of flumaxenil The result were as follows: 1) Systolic and diastolic blood pressure and heart rate were not changed significantly, except diastolic blood pressure decreased significantly (p<0.05) in group II, after intravenous administration of midazolam and diazepam. But these were all increased significantly (p<0.001) after endotracheal intubation in all groups. 2) Systolic and diastolic blood preasure and heart rate were not changed significantly after intravenous administration of flumazenil in group I, II and there were no significant differences between each groups. 3) Tidal volume was increased significantly (p<0.05) in group 1 from 15 min after administration of flumazenil. There were no significant changes in all groups in respiratory rate. SaO2 was increased significantly (p<0.05, p<0.001) in group I, II from 5 min after administration of flumazenil. But it was increased significantly (p<0.05) in group III from 20 min after administration of normal saline too. EtCO2 was decreased insignificantly in all groups. 4) Recovery from anesthesia according to Modified Steward Coma Scale was much improved immediately after administration of flumazenil and was significant (p<0.001) statistically in group I, II from 5 min after administration of flumazenil and reached complete recovery from 20 min after administration of flumaxenil. It was increased gradually and become significant in group III from 10 min after administration of normal saline. These changes of group I, II were significant (p<0.05) compared with group III and reached complete recovery from 60 min after administration of flumazenil.
Administration, Intravenous ; Anesthesia ; Anesthesia, General ; Benzodiazepines ; Blood Pressure ; Coma ; Diazepam ; Flumazenil* ; Heart Rate ; Humans ; Intubation, Intratracheal ; Midazolam* ; Recovery Room ; Respiratory Rate ; Tidal Volume

BACKGROUND/AIMS: Flumazenil was administered after the completion of endoscopy under sedation to reduce recovery time and increase patient safety. We evaluated patient satisfaction after endoscopy under sedation according to the timing of a postprocedural flumazenil injection. METHODS: In total, 200 subjects undergoing concurrent colonoscopy and upper endoscopy while sedated with midazolam and meperidine were enrolled in our investigation. We randomly administered 0.3 mg of flumazenil either immediately or 15 minutes after the endoscopic procedure. A postprocedural questionnaire and next day telephone interview were conducted to assess patient satisfaction. RESULTS: Flumazenil injection timing did not affect the time spent in the recovery room when comparing the two groups of patients. However, the subjects in the 15 minutes injection group were more satisfied with undergoing endoscopy under sedation than the patients in the immediate injection group according to the postprocedural survey (p=0.019). However, no difference in overall satisfaction, memory, or willingness to undergo a future endoscopy was observed between the two groups when the telephone survey was conducted on the following day. CONCLUSIONS: This study demonstrated that a delayed flumazenil injection after endoscopic sedation increased patient satisfaction without prolonging recovery time, even though the benefit of the delayed flumazenil injection did not persist into the following day.
Adult ; Anesthesia Recovery Period ; Endoscopy/adverse effects ; Female ; Flumazenil/*administration & dosage ; GABA Modulators/*administration & dosage ; Humans ; Male ; Memory/drug effects ; Middle Aged ; Pain/epidemiology ; *Patient Satisfaction ; Prospective Studies ; Time Factors ; Treatment Outcome