TY  - JOUR
AU  - Timić-Stamenić, Tamara
AU  - Poe, Michael M.
AU  - Rehman, Sabah
AU  - Santrač, Anja
AU  - Divović, Branka
AU  - Scholze, Petra
AU  - Ernst, Margot
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2631
AB  - We have synthesized and characterized MP-III-022 ((R)-8-ethynyl 6 (2 fluorophenyl)-N,4-dimethyl4H-benzo[f]imidazo[1,5-alpha][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy selective positive allosteric modulator of GABA(A) receptors containing the alpha 5 subunit (alpha 5GABA(A)Rs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 110 mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of alpha 5 beta gamma 2 GABA(A) receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2'F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200 mg/kg), but at the price of activating non-alpha 5 GABA(A)Rs as well as the desired alpha 5GABA(A)Rs at the highest dose. At the dose of 10 mg/kg, which elicits a strong positive modulation of alpha 5GABA(A)Rs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10 mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of alpha 5GABA(A)Rs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmacology
T1  - Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABA(A) receptors containing the alpha 5 subunit
VL  - 791
SP  - 433
EP  - 443
DO  - 10.1016/j.ejphar.2016.09.016
ER  - 

@article{
author = "Timić-Stamenić, Tamara and Poe, Michael M. and Rehman, Sabah and Santrač, Anja and Divović, Branka and Scholze, Petra and Ernst, Margot and Cook, James M. and Savić, Miroslav",
year = "2016",
abstract = "We have synthesized and characterized MP-III-022 ((R)-8-ethynyl 6 (2 fluorophenyl)-N,4-dimethyl4H-benzo[f]imidazo[1,5-alpha][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy selective positive allosteric modulator of GABA(A) receptors containing the alpha 5 subunit (alpha 5GABA(A)Rs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 110 mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of alpha 5 beta gamma 2 GABA(A) receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2'F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200 mg/kg), but at the price of activating non-alpha 5 GABA(A)Rs as well as the desired alpha 5GABA(A)Rs at the highest dose. At the dose of 10 mg/kg, which elicits a strong positive modulation of alpha 5GABA(A)Rs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10 mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of alpha 5GABA(A)Rs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmacology",
title = "Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABA(A) receptors containing the alpha 5 subunit",
volume = "791",
pages = "433-443",
doi = "10.1016/j.ejphar.2016.09.016"
}

Timić-Stamenić, T., Poe, M. M., Rehman, S., Santrač, A., Divović, B., Scholze, P., Ernst, M., Cook, J. M.,& Savić, M.. (2016). Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABA(A) receptors containing the alpha 5 subunit. in European Journal of Pharmacology
Elsevier Science BV, Amsterdam., 791, 433-443.
https://doi.org/10.1016/j.ejphar.2016.09.016

Timić-Stamenić T, Poe MM, Rehman S, Santrač A, Divović B, Scholze P, Ernst M, Cook JM, Savić M. Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABA(A) receptors containing the alpha 5 subunit. in European Journal of Pharmacology. 2016;791:433-443.
doi:10.1016/j.ejphar.2016.09.016 .

Timić-Stamenić, Tamara, Poe, Michael M., Rehman, Sabah, Santrač, Anja, Divović, Branka, Scholze, Petra, Ernst, Margot, Cook, James M., Savić, Miroslav, "Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABA(A) receptors containing the alpha 5 subunit" in European Journal of Pharmacology, 791 (2016):433-443,
https://doi.org/10.1016/j.ejphar.2016.09.016 . .

TY  - CONF
AU  - Batinić, Bojan
AU  - Stanković, Tamara
AU  - Poe, Michael M.
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2654
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Attaining in vivo selectivity of positive modulation of GABAA ɑ3 receptors in rats: a hard task
VL  - 26
IS  - Supplement 2
SP  - S290
EP  - S291
DO  - 10.1016/S0924-977X(16)31186-5
ER  - 

@conference{
author = "Batinić, Bojan and Stanković, Tamara and Poe, Michael M. and Cook, James M. and Savić, Miroslav",
year = "2016",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Attaining in vivo selectivity of positive modulation of GABAA ɑ3 receptors in rats: a hard task",
volume = "26",
number = "Supplement 2",
pages = "S290-S291",
doi = "10.1016/S0924-977X(16)31186-5"
}

Batinić, B., Stanković, T., Poe, M. M., Cook, J. M.,& Savić, M.. (2016). Attaining in vivo selectivity of positive modulation of GABAA ɑ3 receptors in rats: a hard task. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 26(Supplement 2), S290-S291.
https://doi.org/10.1016/S0924-977X(16)31186-5

Batinić B, Stanković T, Poe MM, Cook JM, Savić M. Attaining in vivo selectivity of positive modulation of GABAA ɑ3 receptors in rats: a hard task. in European Neuropsychopharmacology. 2016;26(Supplement 2):S290-S291.
doi:10.1016/S0924-977X(16)31186-5 .

Batinić, Bojan, Stanković, Tamara, Poe, Michael M., Cook, James M., Savić, Miroslav, "Attaining in vivo selectivity of positive modulation of GABAA ɑ3 receptors in rats: a hard task" in European Neuropsychopharmacology, 26, no. Supplement 2 (2016):S290-S291,
https://doi.org/10.1016/S0924-977X(16)31186-5 . .

TY  - JOUR
AU  - Piantadosi, Sean C.
AU  - French, Beverly J.
AU  - Poe, Michael M.
AU  - Timić, Tamara
AU  - Marković, Bojan
AU  - Pabba, Mohan
AU  - Seney, Marianne L.
AU  - Oh, Hyunjung
AU  - Orser, Beverley A.
AU  - Savić, Miroslav
AU  - Cook, James M.
AU  - Sibille, Etienne
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2633
AB  - Rationale: Current first-line treatments for stress related disorders such as major depressive disorder (MDD) act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates. Recent research has implicated the GABAergic system in the pathophysiology of depression, including deficits in interneurons targeting the dendritic compartment of cortical pyramidal cells. Objectives: The present study evaluates whether SH-053-2'F-R-CH3 (denoted "alpha 5-PAM"), a positive allosteric modulator selective for (alpha 5-subunit containing GABA(A) receptors found predominantly on cortical pyramidal cell dendrites, has anti stress effects. Methods: Female and male C57BL6/J mice were exposed to unpredictable chronic mild stress (UCMS) and treated with alpha 5-PAM acutely (30 min prior to assessing behavior) or chronically before being assessed behaviorally. Results: Acute and chronic alpha 5-PAM treatments produce a pattern of decreased stress induced behaviors (denoted as "behavioral emotionality") across various tests in female, but not in male mice. Behavioral Z-scores calculated across a panel of tests designed to best model the range and heterogeneity of human symptomatology confirmed that acute and chronic alpha 5-PAM treatments consistently produce significant decreases in behavioral emotionality in several independent cohorts of females. The behavioral responses to alpha 5-PAM could not be completely accounted for by differences in drug brain disposition between female and male mice. In mice exposed to UCMS, expression of the Gabra5 gene was increased in the frontal cortex after acute treatment and in the hippocampus after chronic treatment with alpha 5-PAM in females only, and these expression changes correlated with behavioral emotionality. Conclusion: We showed that acute and chronic positive modulation of alpha 5 subunit containing GABA(A) receptors elicit anti-stress effects in a sex-dependent manner, suggesting novel therapeutic modalities.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Pharmacology
T1  - Sex-Dependent Anti-Stress Effect of an alpha 5 Subunit Containing GABA(A) Receptor Positive Allosteric Modulator
VL  - 7
DO  - 10.3389/fphar.2016.00446
ER  - 

@article{
author = "Piantadosi, Sean C. and French, Beverly J. and Poe, Michael M. and Timić, Tamara and Marković, Bojan and Pabba, Mohan and Seney, Marianne L. and Oh, Hyunjung and Orser, Beverley A. and Savić, Miroslav and Cook, James M. and Sibille, Etienne",
year = "2016",
abstract = "Rationale: Current first-line treatments for stress related disorders such as major depressive disorder (MDD) act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates. Recent research has implicated the GABAergic system in the pathophysiology of depression, including deficits in interneurons targeting the dendritic compartment of cortical pyramidal cells. Objectives: The present study evaluates whether SH-053-2'F-R-CH3 (denoted "alpha 5-PAM"), a positive allosteric modulator selective for (alpha 5-subunit containing GABA(A) receptors found predominantly on cortical pyramidal cell dendrites, has anti stress effects. Methods: Female and male C57BL6/J mice were exposed to unpredictable chronic mild stress (UCMS) and treated with alpha 5-PAM acutely (30 min prior to assessing behavior) or chronically before being assessed behaviorally. Results: Acute and chronic alpha 5-PAM treatments produce a pattern of decreased stress induced behaviors (denoted as "behavioral emotionality") across various tests in female, but not in male mice. Behavioral Z-scores calculated across a panel of tests designed to best model the range and heterogeneity of human symptomatology confirmed that acute and chronic alpha 5-PAM treatments consistently produce significant decreases in behavioral emotionality in several independent cohorts of females. The behavioral responses to alpha 5-PAM could not be completely accounted for by differences in drug brain disposition between female and male mice. In mice exposed to UCMS, expression of the Gabra5 gene was increased in the frontal cortex after acute treatment and in the hippocampus after chronic treatment with alpha 5-PAM in females only, and these expression changes correlated with behavioral emotionality. Conclusion: We showed that acute and chronic positive modulation of alpha 5 subunit containing GABA(A) receptors elicit anti-stress effects in a sex-dependent manner, suggesting novel therapeutic modalities.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Pharmacology",
title = "Sex-Dependent Anti-Stress Effect of an alpha 5 Subunit Containing GABA(A) Receptor Positive Allosteric Modulator",
volume = "7",
doi = "10.3389/fphar.2016.00446"
}

Piantadosi, S. C., French, B. J., Poe, M. M., Timić, T., Marković, B., Pabba, M., Seney, M. L., Oh, H., Orser, B. A., Savić, M., Cook, J. M.,& Sibille, E.. (2016). Sex-Dependent Anti-Stress Effect of an alpha 5 Subunit Containing GABA(A) Receptor Positive Allosteric Modulator. in Frontiers in Pharmacology
Frontiers Media Sa, Lausanne., 7.
https://doi.org/10.3389/fphar.2016.00446

Piantadosi SC, French BJ, Poe MM, Timić T, Marković B, Pabba M, Seney ML, Oh H, Orser BA, Savić M, Cook JM, Sibille E. Sex-Dependent Anti-Stress Effect of an alpha 5 Subunit Containing GABA(A) Receptor Positive Allosteric Modulator. in Frontiers in Pharmacology. 2016;7.
doi:10.3389/fphar.2016.00446 .

Piantadosi, Sean C., French, Beverly J., Poe, Michael M., Timić, Tamara, Marković, Bojan, Pabba, Mohan, Seney, Marianne L., Oh, Hyunjung, Orser, Beverley A., Savić, Miroslav, Cook, James M., Sibille, Etienne, "Sex-Dependent Anti-Stress Effect of an alpha 5 Subunit Containing GABA(A) Receptor Positive Allosteric Modulator" in Frontiers in Pharmacology, 7 (2016),
https://doi.org/10.3389/fphar.2016.00446 . .

TY  - CONF
AU  - Timić-Stamenić, Tamara
AU  - Santrač, Anja
AU  - Divović, Branka
AU  - Poe, Michael M.
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2424
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Effects of positive alpha5-selective
modulation of GABA A receptors on
amphetamine-induced hyperlocomotion
VL  - 25
IS  - Supplement 1
SP  - S38
EP  - S39
DO  - 10.1016/S0924-977X(15)30007-9
ER  - 

@conference{
author = "Timić-Stamenić, Tamara and Santrač, Anja and Divović, Branka and Poe, Michael M. and Cook, James M. and Savić, Miroslav",
year = "2015",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Effects of positive alpha5-selective
modulation of GABA A receptors on
amphetamine-induced hyperlocomotion",
volume = "25",
number = "Supplement 1",
pages = "S38-S39",
doi = "10.1016/S0924-977X(15)30007-9"
}

Timić-Stamenić, T., Santrač, A., Divović, B., Poe, M. M., Cook, J. M.,& Savić, M.. (2015). Effects of positive alpha5-selective
modulation of GABA A receptors on
amphetamine-induced hyperlocomotion. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 25(Supplement 1), S38-S39.
https://doi.org/10.1016/S0924-977X(15)30007-9

Timić-Stamenić T, Santrač A, Divović B, Poe MM, Cook JM, Savić M. Effects of positive alpha5-selective
modulation of GABA A receptors on
amphetamine-induced hyperlocomotion. in European Neuropsychopharmacology. 2015;25(Supplement 1):S38-S39.
doi:10.1016/S0924-977X(15)30007-9 .

Timić-Stamenić, Tamara, Santrač, Anja, Divović, Branka, Poe, Michael M., Cook, James M., Savić, Miroslav, "Effects of positive alpha5-selective
modulation of GABA A receptors on
amphetamine-induced hyperlocomotion" in European Neuropsychopharmacology, 25, no. Supplement 1 (2015):S38-S39,
https://doi.org/10.1016/S0924-977X(15)30007-9 . .

TY  - CONF
AU  - Timić-Stamenić, Tamara
AU  - Santrač, Anja
AU  - Divović, Branka
AU  - Poe, Michael M.
AU  - James, C. M.
AU  - Savić, Miroslav
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2305
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Effects of positive α5-selective modulation of GABAA receptors on amphetamine-induced hyperactivation
VL  - 25
SP  - S287
EP  - S288
DO  - 10.1016/S0924-977X(15)30342-4
ER  - 

@conference{
author = "Timić-Stamenić, Tamara and Santrač, Anja and Divović, Branka and Poe, Michael M. and James, C. M. and Savić, Miroslav",
year = "2015",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Effects of positive α5-selective modulation of GABAA receptors on amphetamine-induced hyperactivation",
volume = "25",
pages = "S287-S288",
doi = "10.1016/S0924-977X(15)30342-4"
}

Timić-Stamenić, T., Santrač, A., Divović, B., Poe, M. M., James, C. M.,& Savić, M.. (2015). Effects of positive α5-selective modulation of GABAA receptors on amphetamine-induced hyperactivation. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 25, S287-S288.
https://doi.org/10.1016/S0924-977X(15)30342-4

Timić-Stamenić T, Santrač A, Divović B, Poe MM, James CM, Savić M. Effects of positive α5-selective modulation of GABAA receptors on amphetamine-induced hyperactivation. in European Neuropsychopharmacology. 2015;25:S287-S288.
doi:10.1016/S0924-977X(15)30342-4 .

Timić-Stamenić, Tamara, Santrač, Anja, Divović, Branka, Poe, Michael M., James, C. M., Savić, Miroslav, "Effects of positive α5-selective modulation of GABAA receptors on amphetamine-induced hyperactivation" in European Neuropsychopharmacology, 25 (2015):S287-S288,
https://doi.org/10.1016/S0924-977X(15)30342-4 . .

TY  - CONF
AU  - Poe, Michael M.
AU  - Gallos, George
AU  - Puthenkalam, Roshan
AU  - Savić, Miroslav
AU  - Emala, Charles
AU  - Ernst, Margot
AU  - Cook, James M.
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2510
PB  - Amer Chemical Soc, Washington
C3  - Abstracts of Papers of the American Chemical Society
T1  - Imidazobenzodiazepines for improving alpha 5-GABAAR subtype selectivity and their pharmacological relevance
VL  - 250
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2510
ER  - 

@conference{
author = "Poe, Michael M. and Gallos, George and Puthenkalam, Roshan and Savić, Miroslav and Emala, Charles and Ernst, Margot and Cook, James M.",
year = "2015",
publisher = "Amer Chemical Soc, Washington",
journal = "Abstracts of Papers of the American Chemical Society",
title = "Imidazobenzodiazepines for improving alpha 5-GABAAR subtype selectivity and their pharmacological relevance",
volume = "250",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2510"
}

Poe, M. M., Gallos, G., Puthenkalam, R., Savić, M., Emala, C., Ernst, M.,& Cook, J. M.. (2015). Imidazobenzodiazepines for improving alpha 5-GABAAR subtype selectivity and their pharmacological relevance. in Abstracts of Papers of the American Chemical Society
Amer Chemical Soc, Washington., 250.
https://hdl.handle.net/21.15107/rcub_farfar_2510

Poe MM, Gallos G, Puthenkalam R, Savić M, Emala C, Ernst M, Cook JM. Imidazobenzodiazepines for improving alpha 5-GABAAR subtype selectivity and their pharmacological relevance. in Abstracts of Papers of the American Chemical Society. 2015;250.
https://hdl.handle.net/21.15107/rcub_farfar_2510 .

Poe, Michael M., Gallos, George, Puthenkalam, Roshan, Savić, Miroslav, Emala, Charles, Ernst, Margot, Cook, James M., "Imidazobenzodiazepines for improving alpha 5-GABAAR subtype selectivity and their pharmacological relevance" in Abstracts of Papers of the American Chemical Society, 250 (2015),
https://hdl.handle.net/21.15107/rcub_farfar_2510 .

TY  - JOUR
AU  - Clayton, Terry
AU  - Poe, Michael M.
AU  - Rallapalli, Sundari
AU  - Biawat, Poonam
AU  - Savić, Miroslav
AU  - Rowlett, James K.
AU  - Gallos, George
AU  - Emala, Charles
AU  - Kaczorowski, Catherine C.
AU  - Stafford, Douglas C.
AU  - Arnold, Leggy
AU  - Cook, James M.
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2317
AB  - An updated model of the GABA(A) benzodiazepine receptor pharmacophore of the alpha 5-BzR/GABA(A) subtype has been constructed prompted by the synthesis of subtype selective ligands in light of the recent developments in both ligand synthesis, behavioral studies, and molecular modeling studies of the binding site itself. A number of BzR/GABA(A) alpha 5 subtype selective compounds were synthesized, notably alpha 5-subtype selective inverse agonist PWZ-029 (1) which is active in enhancing cognition in both rodents and primates. In addition, a chiral positive allosteric modulator (PAM), SH-053-2'F-R-CH3 (2), has been shown to reverse the deleterious effects in the MAM-model of schizophrenia as well as alleviate constriction in airway smooth muscle. Presented here is an updated model of the pharmacophore for alpha 5 beta 2 gamma 2 Bz/GABA(A) receptors, including a rendering of PWZ-029 docked within the alpha 5-binding pocket showing specific interactions of the molecule with the receptor. Differences in the included volume as compared to alpha 1 beta 2 gamma 2, alpha 2 beta 2 gamma 2, and alpha 3 beta 2 gamma 2 will be illustrated for clarity. These new models enhance the ability to understand structural characteristics of ligands which act as agonists, antagonists, or inverse agonists at the Bz BS of GABA(A) receptors.
PB  - Hindawi Ltd, London
T2  - International Journal of Medicinal Chemistry
T1  - A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model
DO  - 10.1155/2015/430248
ER  - 

@article{
author = "Clayton, Terry and Poe, Michael M. and Rallapalli, Sundari and Biawat, Poonam and Savić, Miroslav and Rowlett, James K. and Gallos, George and Emala, Charles and Kaczorowski, Catherine C. and Stafford, Douglas C. and Arnold, Leggy and Cook, James M.",
year = "2015",
abstract = "An updated model of the GABA(A) benzodiazepine receptor pharmacophore of the alpha 5-BzR/GABA(A) subtype has been constructed prompted by the synthesis of subtype selective ligands in light of the recent developments in both ligand synthesis, behavioral studies, and molecular modeling studies of the binding site itself. A number of BzR/GABA(A) alpha 5 subtype selective compounds were synthesized, notably alpha 5-subtype selective inverse agonist PWZ-029 (1) which is active in enhancing cognition in both rodents and primates. In addition, a chiral positive allosteric modulator (PAM), SH-053-2'F-R-CH3 (2), has been shown to reverse the deleterious effects in the MAM-model of schizophrenia as well as alleviate constriction in airway smooth muscle. Presented here is an updated model of the pharmacophore for alpha 5 beta 2 gamma 2 Bz/GABA(A) receptors, including a rendering of PWZ-029 docked within the alpha 5-binding pocket showing specific interactions of the molecule with the receptor. Differences in the included volume as compared to alpha 1 beta 2 gamma 2, alpha 2 beta 2 gamma 2, and alpha 3 beta 2 gamma 2 will be illustrated for clarity. These new models enhance the ability to understand structural characteristics of ligands which act as agonists, antagonists, or inverse agonists at the Bz BS of GABA(A) receptors.",
publisher = "Hindawi Ltd, London",
journal = "International Journal of Medicinal Chemistry",
title = "A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model",
doi = "10.1155/2015/430248"
}

Clayton, T., Poe, M. M., Rallapalli, S., Biawat, P., Savić, M., Rowlett, J. K., Gallos, G., Emala, C., Kaczorowski, C. C., Stafford, D. C., Arnold, L.,& Cook, J. M.. (2015). A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model. in International Journal of Medicinal Chemistry
Hindawi Ltd, London..
https://doi.org/10.1155/2015/430248

Clayton T, Poe MM, Rallapalli S, Biawat P, Savić M, Rowlett JK, Gallos G, Emala C, Kaczorowski CC, Stafford DC, Arnold L, Cook JM. A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model. in International Journal of Medicinal Chemistry. 2015;.
doi:10.1155/2015/430248 .

Clayton, Terry, Poe, Michael M., Rallapalli, Sundari, Biawat, Poonam, Savić, Miroslav, Rowlett, James K., Gallos, George, Emala, Charles, Kaczorowski, Catherine C., Stafford, Douglas C., Arnold, Leggy, Cook, James M., "A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model" in International Journal of Medicinal Chemistry (2015),
https://doi.org/10.1155/2015/430248 . .

TY  - CONF
AU  - Timić-Stamenić, Tamara
AU  - Joksimović, Srđan
AU  - Milić, Marija
AU  - Batinić, Bojan
AU  - Poe, Michael M.
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2106
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats
VL  - 24
IS  - Supplement 2
SP  - S325
EP  - S325
DO  - 10.1016/S0924-977X(14)70516-4
ER  - 

@conference{
author = "Timić-Stamenić, Tamara and Joksimović, Srđan and Milić, Marija and Batinić, Bojan and Poe, Michael M. and Cook, James M. and Savić, Miroslav",
year = "2014",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats",
volume = "24",
number = "Supplement 2",
pages = "S325-S325",
doi = "10.1016/S0924-977X(14)70516-4"
}

Timić-Stamenić, T., Joksimović, S., Milić, M., Batinić, B., Poe, M. M., Cook, J. M.,& Savić, M.. (2014). Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 24(Supplement 2), S325-S325.
https://doi.org/10.1016/S0924-977X(14)70516-4

Timić-Stamenić T, Joksimović S, Milić M, Batinić B, Poe MM, Cook JM, Savić M. Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats. in European Neuropsychopharmacology. 2014;24(Supplement 2):S325-S325.
doi:10.1016/S0924-977X(14)70516-4 .

Timić-Stamenić, Tamara, Joksimović, Srđan, Milić, Marija, Batinić, Bojan, Poe, Michael M., Cook, James M., Savić, Miroslav, "Positive modulation at alpha(5)GABA(A) receptors is not beneficial for cognitive deficits induced by MK-801 in water maze in rats" in European Neuropsychopharmacology, 24, no. Supplement 2 (2014):S325-S325,
https://doi.org/10.1016/S0924-977X(14)70516-4 . .

TY  - JOUR
AU  - Obradović, Aleksandar
AU  - Joksimović, Srđan
AU  - Poe, Michael M.
AU  - Ramerstorfer, Joachim
AU  - Varagić, Zdravko
AU  - Namjoshi, Ojas A.
AU  - Batinić, Bojan
AU  - Radulović, Tamara
AU  - Marković, Bojan
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2200
AB  - Enormous progress in understanding the role of four populations of benzodiazepine-sensitive GABA(A) receptors was paralleled by the puzzling findings suggesting that substantial separation of behavioral effects may be accomplished by apparently nonselective modulators. We report on SH-I-048A, a newly synthesized chiral positive modulator of GABAA receptors characterized by exceptional subnanomolar affinity, high efficacy and non-selectivity. Its influence on behavior was assessed in Wistar rats and contrasted to that obtained with 2 mg/kg diazepam. SH-I-048A reached micromolar concentrations in brain tissue, while the unbound fraction in brain homogenate was around 1.5%. The approximated electrophysiological responses, which estimated free concentrations of SH-I-048A or diazepam are able to elicit, suggested a similarity between the 10 mg/kg dose of the novel ligand and 2 mg/kg diazepam; however, SH-I-048A was relatively more active at and as-containing GABAA receptors. Behaviorally, SH-I-048A induced sedative, muscle relaxant and ataxic effects, reversed mechanical hyperalgesia 24 h after injury, while it was devoid of clear anxiolytic actions and did not affect water-maze performance. While lack of clear anxiolytic actions may be connected with an enhanced potentiation at al-containing GABAA receptors, the observed behavior in the rotarod, water maze and peripheral nerve injury tests was possibly affected by its prominent action at receptors containing the as subunit. The current results encourage further innovative approaches aimed at linking in vitro an in vivo data in order to help define fine-tuning mechanisms at four sensitive receptor populations that underlie subtle differences in behavioral profiles of benzodiazepine site ligands.
PB  - Elsevier Science BV, Amsterdam
T2  - Brain Research
T1  - Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects
VL  - 1554
SP  - 36
EP  - 48
DO  - 10.1016/j.brainres.2014.01.036
ER  - 

@article{
author = "Obradović, Aleksandar and Joksimović, Srđan and Poe, Michael M. and Ramerstorfer, Joachim and Varagić, Zdravko and Namjoshi, Ojas A. and Batinić, Bojan and Radulović, Tamara and Marković, Bojan and Roth, Brian L. and Sieghart, Werner and Cook, James M. and Savić, Miroslav",
year = "2014",
abstract = "Enormous progress in understanding the role of four populations of benzodiazepine-sensitive GABA(A) receptors was paralleled by the puzzling findings suggesting that substantial separation of behavioral effects may be accomplished by apparently nonselective modulators. We report on SH-I-048A, a newly synthesized chiral positive modulator of GABAA receptors characterized by exceptional subnanomolar affinity, high efficacy and non-selectivity. Its influence on behavior was assessed in Wistar rats and contrasted to that obtained with 2 mg/kg diazepam. SH-I-048A reached micromolar concentrations in brain tissue, while the unbound fraction in brain homogenate was around 1.5%. The approximated electrophysiological responses, which estimated free concentrations of SH-I-048A or diazepam are able to elicit, suggested a similarity between the 10 mg/kg dose of the novel ligand and 2 mg/kg diazepam; however, SH-I-048A was relatively more active at and as-containing GABAA receptors. Behaviorally, SH-I-048A induced sedative, muscle relaxant and ataxic effects, reversed mechanical hyperalgesia 24 h after injury, while it was devoid of clear anxiolytic actions and did not affect water-maze performance. While lack of clear anxiolytic actions may be connected with an enhanced potentiation at al-containing GABAA receptors, the observed behavior in the rotarod, water maze and peripheral nerve injury tests was possibly affected by its prominent action at receptors containing the as subunit. The current results encourage further innovative approaches aimed at linking in vitro an in vivo data in order to help define fine-tuning mechanisms at four sensitive receptor populations that underlie subtle differences in behavioral profiles of benzodiazepine site ligands.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Brain Research",
title = "Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects",
volume = "1554",
pages = "36-48",
doi = "10.1016/j.brainres.2014.01.036"
}

Obradović, A., Joksimović, S., Poe, M. M., Ramerstorfer, J., Varagić, Z., Namjoshi, O. A., Batinić, B., Radulović, T., Marković, B., Roth, B. L., Sieghart, W., Cook, J. M.,& Savić, M.. (2014). Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects. in Brain Research
Elsevier Science BV, Amsterdam., 1554, 36-48.
https://doi.org/10.1016/j.brainres.2014.01.036

Obradović A, Joksimović S, Poe MM, Ramerstorfer J, Varagić Z, Namjoshi OA, Batinić B, Radulović T, Marković B, Roth BL, Sieghart W, Cook JM, Savić M. Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects. in Brain Research. 2014;1554:36-48.
doi:10.1016/j.brainres.2014.01.036 .

Obradović, Aleksandar, Joksimović, Srđan, Poe, Michael M., Ramerstorfer, Joachim, Varagić, Zdravko, Namjoshi, Ojas A., Batinić, Bojan, Radulović, Tamara, Marković, Bojan, Roth, Brian L., Sieghart, Werner, Cook, James M., Savić, Miroslav, "Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: The approximated activation of receptor subtypes may explain behavioral effects" in Brain Research, 1554 (2014):36-48,
https://doi.org/10.1016/j.brainres.2014.01.036 . .

TY  - CONF
AU  - Timić, Tamara
AU  - Joksimović, Srđan
AU  - Obradović, Aleksandar
AU  - Poe, Michael M.
AU  - Biawat, Poonam
AU  - Ramerstorfer, Joachim
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1887
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors
VL  - 23
IS  - Supplement 2
SP  - S259
EP  - S260
DO  - 10.1016/S0924-977X(13)70405-X
ER  - 

@conference{
author = "Timić, Tamara and Joksimović, Srđan and Obradović, Aleksandar and Poe, Michael M. and Biawat, Poonam and Ramerstorfer, Joachim and Roth, Brian L. and Sieghart, Werner and Cook, James M. and Savić, Miroslav",
year = "2013",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors",
volume = "23",
number = "Supplement 2",
pages = "S259-S260",
doi = "10.1016/S0924-977X(13)70405-X"
}

Timić, T., Joksimović, S., Obradović, A., Poe, M. M., Biawat, P., Ramerstorfer, J., Roth, B. L., Sieghart, W., Cook, J. M.,& Savić, M.. (2013). MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 23(Supplement 2), S259-S260.
https://doi.org/10.1016/S0924-977X(13)70405-X

Timić T, Joksimović S, Obradović A, Poe MM, Biawat P, Ramerstorfer J, Roth BL, Sieghart W, Cook JM, Savić M. MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors. in European Neuropsychopharmacology. 2013;23(Supplement 2):S259-S260.
doi:10.1016/S0924-977X(13)70405-X .

Timić, Tamara, Joksimović, Srđan, Obradović, Aleksandar, Poe, Michael M., Biawat, Poonam, Ramerstorfer, Joachim, Roth, Brian L., Sieghart, Werner, Cook, James M., Savić, Miroslav, "MK-801-induced hyperlocomotion in rats is affected by modulation of alpha(5)-containing GABA(A) receptors" in European Neuropsychopharmacology, 23, no. Supplement 2 (2013):S259-S260,
https://doi.org/10.1016/S0924-977X(13)70405-X . .