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Tetsuo Satoh - One of the best experts on this subject based on the ideXlab platform.

  • Flumazenil reduces the Hypnotic Dose of propofol in male patients under spinal anesthesia.
    Journal of anesthesia, 2002
    Co-Authors: Adachi Y, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    Purpose. Flumazenil has been reported to produce a partial benzodiazepine-agonist-like effect in some psychopharmacological examinations. This study investigated the effect of flumazenil on the Hypnotic activity of propofol in 60 men scheduled for minor surgical procedures done under spinal anesthesia. Methods. After a steady state of spinal anesthesia had been reached, patients were pretreated with saline or flumazenil, 5 μg·kg−1, followed by the administration of saline or midazolam, 10 μg·kg−1. Then, 250 μg·kg−1·min−1 of propofol was infused until hypnosis was achieved. Loss of response to a simple command with a slight stimulus, served as the end-point for hypnosis. Immediately after achievement of the end-point, propofol infusion was discontinued, and a 2-ml venous blood sample was obtained from the dorsal pedis vein to determine plasma propofol concentration. Results. Flumazenil significantly decreased the Dose of propofol required and the time required to achieve hypnosis compared with values in the control group (55 ± 10 [mean ± SD] vs 71 ± 14 mg and 212 ± 42 vs 268 ± 48 s, respectively; P < 0.05), whereas flumazenil attenuated the effect of midazolam in reducing the plasma concentration of propofol at hypnosis (2.9 ± 0.5 and 2.5 ± 0.6 μg·ml−1, respectively; P < 0.05). Conclusion. These results suggested that flumazenil may potentiate the Hypnotic properties of propofol, despite flumazenil having an antagonistic effect on the enhanced Hypnotic activity of propofol induced by the coadministration of midazolam.

  • The changes of bispectral index induced by administration of midazolam during propofol anesthesia
    Masui. The Japanese journal of anesthesiology, 2002
    Co-Authors: Maiko Satomoto, Kazuhiko Watanabe, Hideyuki Higuchi, Yushi U Adachi, Hiroshi Aoki, Shigeyuki Yamada, Eiichiro Umeda, Tetsuo Satoh
    Abstract:

    The effect of the additional administration of midazolam or flumazenil on bispectral index (BIS) during propofol anesthesia was investigated in 22 scheduled surgical patients. Midazolam 10 or 30 micrograms.kg-1, or flumazenil 6 or 12 micrograms.kg-1 was injected to the patients to evaluate their effect on BIS after achieving steady state of hypnosis more than 1 hr of propofol anesthesia with 5 mg.kg-1.hr-1. The only midazolam 30 micrograms.kg-1 significantly reduced BIS value from 47.8 +/- 8.6 to 36.8 +/- 6.5. The synergistic interaction between midazolam and propofol assessed by BIS might be less clear than that assessed by Hypnotic Dose of propofol using psychopharmacological investigation.

  • High-Dose flumazenil potentiates the Hypnotic activity of propofol, but not that of thiopental, in ddY mice
    Acta anaesthesiologica Scandinavica, 2001
    Co-Authors: Adachi Y, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    BACKGROUND Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high Dose. This study investigated the effects of flumazenil and midazolam on the Hypnotic Dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the Hypnotic Dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P

  • high Dose flumazenil potentiates the Hypnotic activity of propofol but not that of thiopental in ddy mice
    Acta Anaesthesiologica Scandinavica, 2001
    Co-Authors: Y Adachi, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    BACKGROUND Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high Dose. This study investigated the effects of flumazenil and midazolam on the Hypnotic Dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the Hypnotic Dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P<0.05), but not that of thiopental (9.1+/-0.30 [8.5-9.7] with 0.2 mg kg(-1) flumazenil vs. 9.3+/-0.42 [8.4-10.1] mg kg(-1) with saline). Midazolam reduced the Hypnotic Dose of both propofol and thiopental. Flumazenil antagonized the potentiating effect of midazolam (0.2 mg kg(-1)) on the Hypnotic activity of propofol. CONCLUSIONS These results suggest that the Hypnotic activity of propofol is potentiated by the partial agonist activity of flumazenil in ddY mice.

  • Preliminary report: the effect of flumazenil on the Hypnotic Dose of propofol in ddY mice
    Masui. The Japanese journal of anesthesiology, 2001
    Co-Authors: Adachi Y, Yoshitaka Uchihashi, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    The present investigation dealt with the effect of simultaneous administration of flumazenil on the Hypnotic activity of propofol using a behavioral model of ddY mice. The mixed solution of propofol and flumazenil was administered intravenously into the mice tail vein and the achievement of hypnosis was defined as the loss of the righting reflex. Flumazenil 0.2 mg.kg-1 significantly decreased the required Dose of propofol for hypnosis (8.43 +/- 0.46 mg.kg-1) compared to the control group (10.55 +/- 0.55 mg.kg-1). The mixture with a pH-3.9 acetate buffer solution did not change the Hypnotic Dose of propofol (10.88 +/- 0.62 mg.kg-1). The results suggest that flumazenil might potentiate the Hypnotic activity of propofol in ddY mice.

Zhe-shan Quan - One of the best experts on this subject based on the ideXlab platform.

  • Synthesis and anticonvulsant activity of a new 6-alkoxy-[1,2,4]triazolo[4,3-b]pyridazine
    European journal of medicinal chemistry, 2010
    Co-Authors: Li-ping Guan, Xin Sui, Xian-qing Deng, Ying-chun Quan, Zhe-shan Quan
    Abstract:

    A series of 6-alkoxy-[1,2,4]triazolo[4,3-b]pyridazine derivatives were synthesized. In initial screening and quantitative evaluation, compound 2r was among the most active agents, exhibiting in the same time the lowest toxicity. In the anti-maximal electroshock test, it showed median effective Dose (ED50) of 17.3 mg/kg and median toxicity Dose (TD50) of 380.3 mg/kg, and the protective index (PI) of 22.0, which is much better than PI of the reference drugs. In a subsequent test, compound 2r had median Hypnotic Dose (HD50) of 746.6 mg/kg, thus demonstrating much better margin of safety compared to reference drugs. Compound 2r also showed oral activity against MES-induced seizures and lower oral neurotoxicity. For explanation of the putative mechanism of action, compound 2r was tested in chemical induced models.

  • Anticonvulsant and toxicity evaluation of some 7-alkoxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-ones.
    Bioorganic & medicinal chemistry, 2006
    Co-Authors: Hong-guang Jin, Xian-yu Sun, Kyu-yun Chai, Hu-ri Piao, Zhe-shan Quan
    Abstract:

    Abstract To further investigate anticonvulsant activity of quinoline derivatives, a series of 7-alkoxy-4,5-dihydro-[1,2,4]triazolo[4,3- a ]quinoline-1(2 H )-one derivatives was synthesized starting from 7-hydroxyl-3,4-dihydro-2(1 H )-quinoline. In initial (phase I) screening and quantitative (phase II) evaluation, compound 7-benzyloxyl-4,5-dihydro-[1,2,4]thiazolo[4,3- a ]quinoline-1(2 H )-one ( 3f ) was among the most active but also has the lowest toxicity. In the anti-MES potency test, it showed median effective Dose (ED 50 ) of 12.3 mg/kg, median toxicity Dose (TD 50 ) of 547.5 mg/kg, and the protective index (PI) of 44.5, which is much greater than PI of the prototype drugs phenytoin, phenobarbital, carbamazepin, and valproate. Compound 3f was chosen for further evaluation. In phase III pharmacological test, the compound had median Hypnotic Dose (HD 50 ) and median lethal Dose (LD 50 ) of 1204 mg/kg and >3000 mg/kg, respectively, thus demonstrating much greater margin of safety compared to prototype drugs. The compound 3f also showed significant oral activity against MES-induced seizures and low oral neurotoxicity in mice in phase IV pharmacological test. Possible structure–activity relationship was discussed.

Adachi Y - One of the best experts on this subject based on the ideXlab platform.

  • Flumazenil reduces the Hypnotic Dose of propofol in male patients under spinal anesthesia.
    Journal of anesthesia, 2002
    Co-Authors: Adachi Y, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    Purpose. Flumazenil has been reported to produce a partial benzodiazepine-agonist-like effect in some psychopharmacological examinations. This study investigated the effect of flumazenil on the Hypnotic activity of propofol in 60 men scheduled for minor surgical procedures done under spinal anesthesia. Methods. After a steady state of spinal anesthesia had been reached, patients were pretreated with saline or flumazenil, 5 μg·kg−1, followed by the administration of saline or midazolam, 10 μg·kg−1. Then, 250 μg·kg−1·min−1 of propofol was infused until hypnosis was achieved. Loss of response to a simple command with a slight stimulus, served as the end-point for hypnosis. Immediately after achievement of the end-point, propofol infusion was discontinued, and a 2-ml venous blood sample was obtained from the dorsal pedis vein to determine plasma propofol concentration. Results. Flumazenil significantly decreased the Dose of propofol required and the time required to achieve hypnosis compared with values in the control group (55 ± 10 [mean ± SD] vs 71 ± 14 mg and 212 ± 42 vs 268 ± 48 s, respectively; P < 0.05), whereas flumazenil attenuated the effect of midazolam in reducing the plasma concentration of propofol at hypnosis (2.9 ± 0.5 and 2.5 ± 0.6 μg·ml−1, respectively; P < 0.05). Conclusion. These results suggested that flumazenil may potentiate the Hypnotic properties of propofol, despite flumazenil having an antagonistic effect on the enhanced Hypnotic activity of propofol induced by the coadministration of midazolam.

  • High-Dose flumazenil potentiates the Hypnotic activity of propofol, but not that of thiopental, in ddY mice
    Acta anaesthesiologica Scandinavica, 2001
    Co-Authors: Adachi Y, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    BACKGROUND Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high Dose. This study investigated the effects of flumazenil and midazolam on the Hypnotic Dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the Hypnotic Dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P

  • Preliminary report: the effect of flumazenil on the Hypnotic Dose of propofol in ddY mice
    Masui. The Japanese journal of anesthesiology, 2001
    Co-Authors: Adachi Y, Yoshitaka Uchihashi, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    The present investigation dealt with the effect of simultaneous administration of flumazenil on the Hypnotic activity of propofol using a behavioral model of ddY mice. The mixed solution of propofol and flumazenil was administered intravenously into the mice tail vein and the achievement of hypnosis was defined as the loss of the righting reflex. Flumazenil 0.2 mg.kg-1 significantly decreased the required Dose of propofol for hypnosis (8.43 +/- 0.46 mg.kg-1) compared to the control group (10.55 +/- 0.55 mg.kg-1). The mixture with a pH-3.9 acetate buffer solution did not change the Hypnotic Dose of propofol (10.88 +/- 0.62 mg.kg-1). The results suggest that flumazenil might potentiate the Hypnotic activity of propofol in ddY mice.

  • The determinants of propofol induction of anesthesia Dose.
    Anesthesia and analgesia, 2001
    Co-Authors: Adachi Y, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    Recently it was reported that the pharmacokinetics of propofol are modified by changes in cardiac output. The objective of this study was to evaluate the effects of cardiac output and other factors on the Hypnotic Dose of propofol. One-hundred surgical patients were administered indocyanine green im

  • Small Dose midazolam or droperidol reduces the Hypnotic Dose of propofol at the induction of anaesthesia
    European journal of anaesthesiology, 2000
    Co-Authors: Adachi Y, Yoshitaka Uchihashi, Kazuhiko Watanabe, Tetsuo Satoh
    Abstract:

    We investigated the effect of a small Dose of midazolam, ketamine, droperidol or lidocaine on the propofol Dose required for hypnosis during induction of general anaesthesia. These drugs were randomly administered to 100 patients about to undergo scheduled surgery. Propofol was then infused at a rate of 250 microg kg-1 min-1 and the Hypnotic Dose to produce hypnosis was evaluated. Midazolam (20 microg kg-1) and droperidol (20 microg kg-1) significantly reduced the mean Hypnotic Dose of propofol (mean) S.D.) compared with the placebo (43.7 +/- 17.8 mg, 61.9 +/- 10.6 mg and 72.5 +/- 27.7 mg after pretreatment with midazolam, droperidol and placebo, respectively), whereas ketamine (0.1 mg kg-1) and lidocaine (1 mg kg-1) did not significantly affect the Hypnotic Dose of propofol (63. 1 +/- 25.6 mg and 65.1 +/- 24.8 mg, respectively). Only midazolam when compared with saline administration, (176 +/- 66 s and 298 +/- 126 s, respectively), shortened the time to achieve hypnosis. The changes in blood pressure (non-invasive) and heart rate were not significantly different in all groups during the induction of anaesthesia and oro-tracheal intubation. These results raise the possibility that new combinations of central nervous system drugs, such as droperidol and propofol, have a potential to reduce the Dose of intravenous anaesthetics, including propofol, that produce hypnosis without significant adverse effects.

Annemiek Vermeeren - One of the best experts on this subject based on the ideXlab platform.

  • Residual Effects of Hypnotics
    CNS Drugs, 2004
    Co-Authors: Annemiek Vermeeren
    Abstract:

    The risk of ‘hangover’ effects, e.g. residual daytime sleepiness and impairment of psychomotor and cognitive functioning the day after bedtime administration, is one of the main problems associated with the use of Hypnotics. However, the severity and duration of these effects varies considerably between Hypnotics and is strongly dependent on the Dose administered. This article reviews epidemiological evidence on the effect of Hypnotics on patients’ risk for accidents such as traffic accidents, falls and hip fractures (i.e. end-points for residual effects). Information on the duration and severity of residual effects of 11 Hypnotics (flunitrazepam, flurazepam, loprazolam, lormetazepam, midazolam, nitrazepam, temazepam, triazolam, zaleplon, zolpidem and zopiclone) was derived from expert ratings, a meta-analysis and actual driving studies. Epidemiological studies show that the risks of an accident increase with increasing half-life of the Hypnotic, but that the use of Hypnotics with a short half-life, such as triazolam, zopiclone and zolpidem, can also be associated with increased risks. A summary of results from experimental studies should enable prescribing clinicians to compare residual effects of the various Hypnotics at different Doses and select the one considered most favourable in this respect for the individual patient. This information should also enable them to inform patients more adequately about the likelihood and duration of residual effects of a specific Hypnotic Dose.

Kazuhiko Watanabe - One of the best experts on this subject based on the ideXlab platform.

  • Flumazenil reduces the Hypnotic Dose of propofol in male patients under spinal anesthesia.
    Journal of anesthesia, 2002
    Co-Authors: Adachi Y, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    Purpose. Flumazenil has been reported to produce a partial benzodiazepine-agonist-like effect in some psychopharmacological examinations. This study investigated the effect of flumazenil on the Hypnotic activity of propofol in 60 men scheduled for minor surgical procedures done under spinal anesthesia. Methods. After a steady state of spinal anesthesia had been reached, patients were pretreated with saline or flumazenil, 5 μg·kg−1, followed by the administration of saline or midazolam, 10 μg·kg−1. Then, 250 μg·kg−1·min−1 of propofol was infused until hypnosis was achieved. Loss of response to a simple command with a slight stimulus, served as the end-point for hypnosis. Immediately after achievement of the end-point, propofol infusion was discontinued, and a 2-ml venous blood sample was obtained from the dorsal pedis vein to determine plasma propofol concentration. Results. Flumazenil significantly decreased the Dose of propofol required and the time required to achieve hypnosis compared with values in the control group (55 ± 10 [mean ± SD] vs 71 ± 14 mg and 212 ± 42 vs 268 ± 48 s, respectively; P < 0.05), whereas flumazenil attenuated the effect of midazolam in reducing the plasma concentration of propofol at hypnosis (2.9 ± 0.5 and 2.5 ± 0.6 μg·ml−1, respectively; P < 0.05). Conclusion. These results suggested that flumazenil may potentiate the Hypnotic properties of propofol, despite flumazenil having an antagonistic effect on the enhanced Hypnotic activity of propofol induced by the coadministration of midazolam.

  • The changes of bispectral index induced by administration of midazolam during propofol anesthesia
    Masui. The Japanese journal of anesthesiology, 2002
    Co-Authors: Maiko Satomoto, Kazuhiko Watanabe, Hideyuki Higuchi, Yushi U Adachi, Hiroshi Aoki, Shigeyuki Yamada, Eiichiro Umeda, Tetsuo Satoh
    Abstract:

    The effect of the additional administration of midazolam or flumazenil on bispectral index (BIS) during propofol anesthesia was investigated in 22 scheduled surgical patients. Midazolam 10 or 30 micrograms.kg-1, or flumazenil 6 or 12 micrograms.kg-1 was injected to the patients to evaluate their effect on BIS after achieving steady state of hypnosis more than 1 hr of propofol anesthesia with 5 mg.kg-1.hr-1. The only midazolam 30 micrograms.kg-1 significantly reduced BIS value from 47.8 +/- 8.6 to 36.8 +/- 6.5. The synergistic interaction between midazolam and propofol assessed by BIS might be less clear than that assessed by Hypnotic Dose of propofol using psychopharmacological investigation.

  • High-Dose flumazenil potentiates the Hypnotic activity of propofol, but not that of thiopental, in ddY mice
    Acta anaesthesiologica Scandinavica, 2001
    Co-Authors: Adachi Y, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    BACKGROUND Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high Dose. This study investigated the effects of flumazenil and midazolam on the Hypnotic Dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the Hypnotic Dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P

  • high Dose flumazenil potentiates the Hypnotic activity of propofol but not that of thiopental in ddy mice
    Acta Anaesthesiologica Scandinavica, 2001
    Co-Authors: Y Adachi, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    BACKGROUND Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high Dose. This study investigated the effects of flumazenil and midazolam on the Hypnotic Dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the Hypnotic Dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P<0.05), but not that of thiopental (9.1+/-0.30 [8.5-9.7] with 0.2 mg kg(-1) flumazenil vs. 9.3+/-0.42 [8.4-10.1] mg kg(-1) with saline). Midazolam reduced the Hypnotic Dose of both propofol and thiopental. Flumazenil antagonized the potentiating effect of midazolam (0.2 mg kg(-1)) on the Hypnotic activity of propofol. CONCLUSIONS These results suggest that the Hypnotic activity of propofol is potentiated by the partial agonist activity of flumazenil in ddY mice.

  • Preliminary report: the effect of flumazenil on the Hypnotic Dose of propofol in ddY mice
    Masui. The Japanese journal of anesthesiology, 2001
    Co-Authors: Adachi Y, Yoshitaka Uchihashi, Kazuhiko Watanabe, Hideyuki Higuchi, Tetsuo Satoh
    Abstract:

    The present investigation dealt with the effect of simultaneous administration of flumazenil on the Hypnotic activity of propofol using a behavioral model of ddY mice. The mixed solution of propofol and flumazenil was administered intravenously into the mice tail vein and the achievement of hypnosis was defined as the loss of the righting reflex. Flumazenil 0.2 mg.kg-1 significantly decreased the required Dose of propofol for hypnosis (8.43 +/- 0.46 mg.kg-1) compared to the control group (10.55 +/- 0.55 mg.kg-1). The mixture with a pH-3.9 acetate buffer solution did not change the Hypnotic Dose of propofol (10.88 +/- 0.62 mg.kg-1). The results suggest that flumazenil might potentiate the Hypnotic activity of propofol in ddY mice.