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Francisco Silveira Guimarães - One of the best experts on this subject based on the ideXlab platform.

  • Benzodiazepine receptor and serotonin 2A receptor modulate the aversive-like effects of nitric oxide in the dorsolateral periaqueductal gray of rats
    Psychopharmacology, 2004
    Co-Authors: Fabrício Araújo Moreira, Francisco Silveira Guimarães
    Abstract:

    Rationale Escape reactions induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) are inhibited by local administration of benzodiazepine (BZ) or serotonin (5-HT) receptor agonists. Nitric oxide (NO) is a gas messenger that may mediate aversive behaviors. NO donors injected into the dlPAG induce escape reactions. Objectives To test the hypothesis that the escape reactions induced by a NO donor in the dlPAG would be attenuated by pre-treatment with BZ-receptor or 5-HT-receptor agonists. Methods Male Wistar rats with cannulae aimed at the dlPAG received microinjections of vehicle (0.2 μl), the BZ Midazolam Maleate (80 nmol), the 5-HT_1A-receptor agonist 8-OH-DPAT (8 nmol or 16 nmol) or the 5-HT_2A/2C-receptor agonist DOI (16 nmol) 10 min before the administration of the NO donor SIN-1 (150 nmol). Behavioral observation took place immediately after the last injection in an open arena over a 10-min period. Results SIN-1 induced escape reactions characterized by running and jumps. Pre-treatment with DOI, but not 8-OH-DPAT, partially inhibited the effects of SIN-1. Pre-treatment with Midazolam Maleate, however, completely prevented the effects of the NO donor. Conclusion The results suggest that the aversive-like effects of NO donor in the dlPAG may be modulated by the BZ and 5-HT_2A/2C receptors.

  • Benzodiazepine receptor and serotonin 2A receptor modulate the aversive-like effects of nitric oxide in the dorsolateral periaqueductal gray of rats.
    Psychopharmacology, 2004
    Co-Authors: Fabrício Araújo Moreira, Francisco Silveira Guimarães
    Abstract:

    Escape reactions induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) are inhibited by local administration of benzodiazepine (BZ) or serotonin (5-HT) receptor agonists. Nitric oxide (NO) is a gas messenger that may mediate aversive behaviors. NO donors injected into the dlPAG induce escape reactions. To test the hypothesis that the escape reactions induced by a NO donor in the dlPAG would be attenuated by pre-treatment with BZ-receptor or 5-HT-receptor agonists. Male Wistar rats with cannulae aimed at the dlPAG received microinjections of vehicle (0.2 microl), the BZ Midazolam Maleate (80 nmol), the 5-HT(1A)-receptor agonist 8-OH-DPAT (8 nmol or 16 nmol) or the 5-HT(2A/2C)-receptor agonist DOI (16 nmol) 10 min before the administration of the NO donor SIN-1 (150 nmol). Behavioral observation took place immediately after the last injection in an open arena over a 10-min period. SIN-1 induced escape reactions characterized by running and jumps. Pre-treatment with DOI, but not 8-OH-DPAT, partially inhibited the effects of SIN-1. Pre-treatment with Midazolam Maleate, however, completely prevented the effects of the NO donor. The results suggest that the aversive-like effects of NO donor in the dlPAG may be modulated by the BZ and 5-HT(2A/2C) receptors.

Fabrício Araújo Moreira - One of the best experts on this subject based on the ideXlab platform.

  • Benzodiazepine receptor and serotonin 2A receptor modulate the aversive-like effects of nitric oxide in the dorsolateral periaqueductal gray of rats
    Psychopharmacology, 2004
    Co-Authors: Fabrício Araújo Moreira, Francisco Silveira Guimarães
    Abstract:

    Rationale Escape reactions induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) are inhibited by local administration of benzodiazepine (BZ) or serotonin (5-HT) receptor agonists. Nitric oxide (NO) is a gas messenger that may mediate aversive behaviors. NO donors injected into the dlPAG induce escape reactions. Objectives To test the hypothesis that the escape reactions induced by a NO donor in the dlPAG would be attenuated by pre-treatment with BZ-receptor or 5-HT-receptor agonists. Methods Male Wistar rats with cannulae aimed at the dlPAG received microinjections of vehicle (0.2 μl), the BZ Midazolam Maleate (80 nmol), the 5-HT_1A-receptor agonist 8-OH-DPAT (8 nmol or 16 nmol) or the 5-HT_2A/2C-receptor agonist DOI (16 nmol) 10 min before the administration of the NO donor SIN-1 (150 nmol). Behavioral observation took place immediately after the last injection in an open arena over a 10-min period. Results SIN-1 induced escape reactions characterized by running and jumps. Pre-treatment with DOI, but not 8-OH-DPAT, partially inhibited the effects of SIN-1. Pre-treatment with Midazolam Maleate, however, completely prevented the effects of the NO donor. Conclusion The results suggest that the aversive-like effects of NO donor in the dlPAG may be modulated by the BZ and 5-HT_2A/2C receptors.

  • Benzodiazepine receptor and serotonin 2A receptor modulate the aversive-like effects of nitric oxide in the dorsolateral periaqueductal gray of rats.
    Psychopharmacology, 2004
    Co-Authors: Fabrício Araújo Moreira, Francisco Silveira Guimarães
    Abstract:

    Escape reactions induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) are inhibited by local administration of benzodiazepine (BZ) or serotonin (5-HT) receptor agonists. Nitric oxide (NO) is a gas messenger that may mediate aversive behaviors. NO donors injected into the dlPAG induce escape reactions. To test the hypothesis that the escape reactions induced by a NO donor in the dlPAG would be attenuated by pre-treatment with BZ-receptor or 5-HT-receptor agonists. Male Wistar rats with cannulae aimed at the dlPAG received microinjections of vehicle (0.2 microl), the BZ Midazolam Maleate (80 nmol), the 5-HT(1A)-receptor agonist 8-OH-DPAT (8 nmol or 16 nmol) or the 5-HT(2A/2C)-receptor agonist DOI (16 nmol) 10 min before the administration of the NO donor SIN-1 (150 nmol). Behavioral observation took place immediately after the last injection in an open arena over a 10-min period. SIN-1 induced escape reactions characterized by running and jumps. Pre-treatment with DOI, but not 8-OH-DPAT, partially inhibited the effects of SIN-1. Pre-treatment with Midazolam Maleate, however, completely prevented the effects of the NO donor. The results suggest that the aversive-like effects of NO donor in the dlPAG may be modulated by the BZ and 5-HT(2A/2C) receptors.

Vera L. Lanchote - One of the best experts on this subject based on the ideXlab platform.

  • Investigation of the in vivo activity of CYP3A in Brazilian volunteers: comparison of Midazolam and omeprazole as drug markers
    European Journal of Clinical Pharmacology, 2008
    Co-Authors: Adriana Rocha, Eduardo B. Coelho, Soraia A. P. Moussa, Vera L. Lanchote
    Abstract:

    Objective This study compares Midazolam with omeprazole as marker drugs for the evaluation of CYP3A activity in nine healthy self-reported white Brazilian volunteers. Methods Omeprazole was also used to evaluate the CYP2C19 phenotype. The volunteers received p.o. 20 mg omeprazole, and blood samples were collected 3.5 h after drug administration. After a washout period of 10 days, the volunteers received p.o. 15 mg Midazolam Maleate, and serial blood samples were collected up to 6 h after administration of the drug. CYP2C19 was genotyped for the allelic variants CYP2C19*1 , CYP2C19*2 , CYP2C19*3 , and CYP2C19*17 . Analysis of omeprazole, hydroxyomeprazole, omeprazole sulfone, and Midazolam in plasma was carried out by LC-MS/MS. Results The volunteers genotyped as CYP2C19*1*17 , CYP2C19*17*17 , CYP2C19*1*1 ( n  = 8), or CYP2C19*17*2 ( n  = 1) presented a median hydroxylation index (omeprazole/hydroxyomeprazole) of 1.35, indicating that all of them were extensive metabolizers of CYP2C19. The volunteers ( n  = 9) presented a 0.12 log of the omeprazole/sulfone ratio and a median oral clearance of Midazolam of 17.89 ml min^−1 kg^−1, suggesting normal CYP3A activity. Conclusions Orthogonal regression analysis between Midazolam clearance and log of the plasma concentrations of the omeprazole/omeprazole sulfone ratio ( R  = −0.7544, P  

Suzanne Higgs - One of the best experts on this subject based on the ideXlab platform.

  • Benzodiazepine effects on licking responses for sodium chloride solutions in water-deprived male rats.
    Physiology & behavior, 2005
    Co-Authors: Steven J. Cooper, Suzanne Higgs
    Abstract:

    Abstract The aim of this study was to investigate, for the first time, the effects of a centrally active benzodiazepine receptor agonist, Midazolam Maleate, on the microstructure of licking responses for a range of sodium chloride (NaCl) solutions in mildly water-deprived male rats. Doses of Midazolam were chosen (0.3–3.0 mg/kg. i.p.) which have been characterised in studies of licking responses for several different kinds of nutrients. NaCl concentrations (0.075 M–0.45 M) were chosen to cover a range of taste preferences and acceptability. A brief-contact testing session was employed to focus on the initial determinants of licking responses (i.e. taste palatability), and to minimise any contribution of postingestional effects. The results indicate the Midazolam significantly increased the total number of licks recorded across all salt concentrations, but that it had no effect on the number of bouts of licking. Instead, Midazolam specifically enhanced the mean duration of licking bouts, an effect that was most evident at the weaker but more acceptable NaCl concentrations (0.075 M and 0.15 M). In addition, Midazolam diminished the intrabout rate of licking across all salt concentrations. These results confirm that benzodiazepines can exert a specific pattern of effects on the microstructure of licking for salt solutions. They are discussed in terms of the oropharyngeal stimulation controlling intake and the palatability or “liking” hypothesis for the effects of benzodiazepines on taste stimuli, and indicate that the hypothesis is applicable to salt solution ingestive behaviour.

Adriana Rocha - One of the best experts on this subject based on the ideXlab platform.

  • Investigation of the in vivo activity of CYP3A in Brazilian volunteers: comparison of Midazolam and omeprazole as drug markers
    European Journal of Clinical Pharmacology, 2008
    Co-Authors: Adriana Rocha, Eduardo B. Coelho, Soraia A. P. Moussa, Vera L. Lanchote
    Abstract:

    Objective This study compares Midazolam with omeprazole as marker drugs for the evaluation of CYP3A activity in nine healthy self-reported white Brazilian volunteers. Methods Omeprazole was also used to evaluate the CYP2C19 phenotype. The volunteers received p.o. 20 mg omeprazole, and blood samples were collected 3.5 h after drug administration. After a washout period of 10 days, the volunteers received p.o. 15 mg Midazolam Maleate, and serial blood samples were collected up to 6 h after administration of the drug. CYP2C19 was genotyped for the allelic variants CYP2C19*1 , CYP2C19*2 , CYP2C19*3 , and CYP2C19*17 . Analysis of omeprazole, hydroxyomeprazole, omeprazole sulfone, and Midazolam in plasma was carried out by LC-MS/MS. Results The volunteers genotyped as CYP2C19*1*17 , CYP2C19*17*17 , CYP2C19*1*1 ( n  = 8), or CYP2C19*17*2 ( n  = 1) presented a median hydroxylation index (omeprazole/hydroxyomeprazole) of 1.35, indicating that all of them were extensive metabolizers of CYP2C19. The volunteers ( n  = 9) presented a 0.12 log of the omeprazole/sulfone ratio and a median oral clearance of Midazolam of 17.89 ml min^−1 kg^−1, suggesting normal CYP3A activity. Conclusions Orthogonal regression analysis between Midazolam clearance and log of the plasma concentrations of the omeprazole/omeprazole sulfone ratio ( R  = −0.7544, P