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  - JOUR
AU  - Timić-Stamenić, Tamara
AU  - Joksimović, Srđan
AU  - Biawat, Poonam
AU  - Stanković, Tamara
AU  - Marković, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2314
AB  - Reportedly, negative modulation of alpha(5) GABA(A) receptors may improve cognition in normal and pharmacologically-impaired animals, and such modulation has been proposed as an avenue for treatment of cognitive symptoms in schizophrenia. This study assessed the actions of PWZ-029, administered at doses (2, 5, and 10 mg/kg) at which it reached micromolar concentrations in brain tissue with estimated free concentrations adequate for selective modulation of alpha(5) GABA(A) receptors, in three cognitive tasks in male Wistar rats acutely treated with the noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801 (0.1 mg/kg), as well in tests of locomotor activity potentiated by MK-801 (0.2 mg/kg) or amphetamine (0.5 mg/kg). In a hormetic-like manner, only 5 mg/kg PWZ-029 reversed MK-801-induced deficits in novel object recognition test (visual recognition memory), whereas in the Morris water maze, the 2 mg/kg dose of PWZ-029 exerted partial beneficial effects on spatial learning impairment. PWZ-029 did not affect recognition memory deficits in social novelty discrimination procedure. Motor hyperactivity induced with MK-801 or amphetamine was not preventable by PWZ-029. Our results show that certain MK-801-induced memory deficits can be ameliorated by negative modulation of alpha(5) GABA(A) receptors, and point to the need for further elucidation of their translational relevance to cognitive deterioration in schizophrenia.
PB  - Sage Publications Ltd, London
T2  - Journal of Psychopharmacology
T1  - Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion
VL  - 29
IS  - 9
SP  - 1013
EP  - 1024
DO  - 10.1177/0269881115590601
ER  - 

@article{
author = "Timić-Stamenić, Tamara and Joksimović, Srđan and Biawat, Poonam and Stanković, Tamara and Marković, Bojan and Cook, James M. and Savić, Miroslav",
year = "2015",
abstract = "Reportedly, negative modulation of alpha(5) GABA(A) receptors may improve cognition in normal and pharmacologically-impaired animals, and such modulation has been proposed as an avenue for treatment of cognitive symptoms in schizophrenia. This study assessed the actions of PWZ-029, administered at doses (2, 5, and 10 mg/kg) at which it reached micromolar concentrations in brain tissue with estimated free concentrations adequate for selective modulation of alpha(5) GABA(A) receptors, in three cognitive tasks in male Wistar rats acutely treated with the noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801 (0.1 mg/kg), as well in tests of locomotor activity potentiated by MK-801 (0.2 mg/kg) or amphetamine (0.5 mg/kg). In a hormetic-like manner, only 5 mg/kg PWZ-029 reversed MK-801-induced deficits in novel object recognition test (visual recognition memory), whereas in the Morris water maze, the 2 mg/kg dose of PWZ-029 exerted partial beneficial effects on spatial learning impairment. PWZ-029 did not affect recognition memory deficits in social novelty discrimination procedure. Motor hyperactivity induced with MK-801 or amphetamine was not preventable by PWZ-029. Our results show that certain MK-801-induced memory deficits can be ameliorated by negative modulation of alpha(5) GABA(A) receptors, and point to the need for further elucidation of their translational relevance to cognitive deterioration in schizophrenia.",
publisher = "Sage Publications Ltd, London",
journal = "Journal of Psychopharmacology",
title = "Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion",
volume = "29",
number = "9",
pages = "1013-1024",
doi = "10.1177/0269881115590601"
}

Timić-Stamenić, T., Joksimović, S., Biawat, P., Stanković, T., Marković, B., Cook, J. M.,& Savić, M.. (2015). Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion. in Journal of Psychopharmacology
Sage Publications Ltd, London., 29(9), 1013-1024.
https://doi.org/10.1177/0269881115590601

Timić-Stamenić T, Joksimović S, Biawat P, Stanković T, Marković B, Cook JM, Savić M. Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion. in Journal of Psychopharmacology. 2015;29(9):1013-1024.
doi:10.1177/0269881115590601 .

Timić-Stamenić, Tamara, Joksimović, Srđan, Biawat, Poonam, Stanković, Tamara, Marković, Bojan, Cook, James M., Savić, Miroslav, "Negative modulation of alpha(5) GABA(A) receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion" in Journal of Psychopharmacology, 29, no. 9 (2015):1013-1024,
https://doi.org/10.1177/0269881115590601 . .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Obradović, Aleksandar
AU  - Timić, Tamara
AU  - Radulović, Tamara
AU  - Biawat, Poonam
AU  - Kovacević, Jovana
AU  - Milić, Marija
AU  - Batinić, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1888
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia
VL  - 23
IS  - Supplement 2
SP  - S260
EP  - S260
DO  - 10.1016/S0924-977X(13)70406-1
ER  - 

@conference{
author = "Joksimović, Srđan and Obradović, Aleksandar and Timić, Tamara and Radulović, Tamara and Biawat, Poonam and Kovacević, Jovana and Milić, Marija and Batinić, Bojan and Cook, James M. and Savić, Miroslav",
year = "2013",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia",
volume = "23",
number = "Supplement 2",
pages = "S260-S260",
doi = "10.1016/S0924-977X(13)70406-1"
}

Joksimović, S., Obradović, A., Timić, T., Radulović, T., Biawat, P., Kovacević, J., Milić, M., Batinić, B., Cook, J. M.,& Savić, M.. (2013). PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 23(Supplement 2), S260-S260.
https://doi.org/10.1016/S0924-977X(13)70406-1

Joksimović S, Obradović A, Timić T, Radulović T, Biawat P, Kovacević J, Milić M, Batinić B, Cook JM, Savić M. PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia. in European Neuropsychopharmacology. 2013;23(Supplement 2):S260-S260.
doi:10.1016/S0924-977X(13)70406-1 .

Joksimović, Srđan, Obradović, Aleksandar, Timić, Tamara, Radulović, Tamara, Biawat, Poonam, Kovacević, Jovana, Milić, Marija, Batinić, Bojan, Cook, James M., Savić, Miroslav, "PWZ-029 alleviates MK-801-induced memory deficits in the rat: implications for the treatment of cognitive impairment in schizophrenia" in European Neuropsychopharmacology, 23, no. Supplement 2 (2013):S260-S260,
https://doi.org/10.1016/S0924-977X(13)70406-1 . .

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 . .

TY  - JOUR
AU  - Milić, Marija
AU  - Timić, Tamara
AU  - Joksimović, Srđan
AU  - Biawat, Poonam
AU  - Rallapalli, Sundari
AU  - Divljaković, Jovana
AU  - Radulović, Tamara
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1926
AB  - Inverse agonism at the benzodiazepine site of alpha(5) subunit-containing GABA(A) receptors is an attractive approach for the development of putative cognition-enhancing compounds, which are still far from clinical application. Several ligands with binding and/or functional selectivity for alpha(5) GABA(A) receptors have been synthesized and tested in a few animal models. PWZ-029 is an alpha(5) GABA(A) selective inverse agonist whose memory enhancing effects were demonstrated in the passive avoidance task in rats and in Pavlovian fear conditioning in mice. In the present study we investigated the effects of PWZ-029 administration in novel object recognition test and Morris water maze, in normal and scopolamine-treated rats. All the three doses of PWZ-029 (2,5 and 10 mg/kg) improved object recognition after the 24-h delay period, as shown by significant differences between the exploration times of the novel and old object, and the respective discrimination indices. PWZ-029 (2 mg/kg) also successfully reversed the 0.3 mg/kg scopolamine-induced deficit in recognition memory after the 1-h delay. In the Morris water maze test, PWZ-029 (5,10 and 15 mg/kg) did not significantly influence swim patterns, either during five acquisition days or during the treatment-free probe trial. PWZ-029 (2, 5 and 10 mg/kg) also proved to be ineffective in the reversal of the 1 mg/kg scopolamine-induced memory impairment in the water maze. The present mixed results encourage use of a variety of tests and experimental conditions in order to increase the predictability of preclinical testing of selective as GABA(A) inverse agonists.
PB  - Elsevier Science BV, Amsterdam
T2  - Behavioural Brain Research
T1  - PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats
VL  - 241
SP  - 206
EP  - 213
DO  - 10.1016/j.bbr.2012.12.016
ER  - 

@article{
author = "Milić, Marija and Timić, Tamara and Joksimović, Srđan and Biawat, Poonam and Rallapalli, Sundari and Divljaković, Jovana and Radulović, Tamara and Cook, James M. and Savić, Miroslav",
year = "2013",
abstract = "Inverse agonism at the benzodiazepine site of alpha(5) subunit-containing GABA(A) receptors is an attractive approach for the development of putative cognition-enhancing compounds, which are still far from clinical application. Several ligands with binding and/or functional selectivity for alpha(5) GABA(A) receptors have been synthesized and tested in a few animal models. PWZ-029 is an alpha(5) GABA(A) selective inverse agonist whose memory enhancing effects were demonstrated in the passive avoidance task in rats and in Pavlovian fear conditioning in mice. In the present study we investigated the effects of PWZ-029 administration in novel object recognition test and Morris water maze, in normal and scopolamine-treated rats. All the three doses of PWZ-029 (2,5 and 10 mg/kg) improved object recognition after the 24-h delay period, as shown by significant differences between the exploration times of the novel and old object, and the respective discrimination indices. PWZ-029 (2 mg/kg) also successfully reversed the 0.3 mg/kg scopolamine-induced deficit in recognition memory after the 1-h delay. In the Morris water maze test, PWZ-029 (5,10 and 15 mg/kg) did not significantly influence swim patterns, either during five acquisition days or during the treatment-free probe trial. PWZ-029 (2, 5 and 10 mg/kg) also proved to be ineffective in the reversal of the 1 mg/kg scopolamine-induced memory impairment in the water maze. The present mixed results encourage use of a variety of tests and experimental conditions in order to increase the predictability of preclinical testing of selective as GABA(A) inverse agonists.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Behavioural Brain Research",
title = "PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats",
volume = "241",
pages = "206-213",
doi = "10.1016/j.bbr.2012.12.016"
}

Milić, M., Timić, T., Joksimović, S., Biawat, P., Rallapalli, S., Divljaković, J., Radulović, T., Cook, J. M.,& Savić, M.. (2013). PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats. in Behavioural Brain Research
Elsevier Science BV, Amsterdam., 241, 206-213.
https://doi.org/10.1016/j.bbr.2012.12.016

Milić M, Timić T, Joksimović S, Biawat P, Rallapalli S, Divljaković J, Radulović T, Cook JM, Savić M. PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats. in Behavioural Brain Research. 2013;241:206-213.
doi:10.1016/j.bbr.2012.12.016 .

Milić, Marija, Timić, Tamara, Joksimović, Srđan, Biawat, Poonam, Rallapalli, Sundari, Divljaković, Jovana, Radulović, Tamara, Cook, James M., Savić, Miroslav, "PWZ-029, an inverse agonist selective for alpha(5) GABA(A) receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats" in Behavioural Brain Research, 241 (2013):206-213,
https://doi.org/10.1016/j.bbr.2012.12.016 . .

TY  - CONF
AU  - Samardžić, Janko
AU  - Batinić, Bojan
AU  - Biawat, Poonam
AU  - Obradović, Dragan I.
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1662
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Acute effects of an inverse agonist selective for alpha(5) GABA(A) receptors on rat behaviour in the forced swim test
VL  - 22
IS  - Supplement 2
SP  - S187
EP  - S188
DO  - 10.1016/S0924-977X(12)70269-9
ER  - 

@conference{
author = "Samardžić, Janko and Batinić, Bojan and Biawat, Poonam and Obradović, Dragan I. and Cook, James M. and Savić, Miroslav",
year = "2012",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Acute effects of an inverse agonist selective for alpha(5) GABA(A) receptors on rat behaviour in the forced swim test",
volume = "22",
number = "Supplement 2",
pages = "S187-S188",
doi = "10.1016/S0924-977X(12)70269-9"
}

Samardžić, J., Batinić, B., Biawat, P., Obradović, D. I., Cook, J. M.,& Savić, M.. (2012). Acute effects of an inverse agonist selective for alpha(5) GABA(A) receptors on rat behaviour in the forced swim test. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 22(Supplement 2), S187-S188.
https://doi.org/10.1016/S0924-977X(12)70269-9

Samardžić J, Batinić B, Biawat P, Obradović DI, Cook JM, Savić M. Acute effects of an inverse agonist selective for alpha(5) GABA(A) receptors on rat behaviour in the forced swim test. in European Neuropsychopharmacology. 2012;22(Supplement 2):S187-S188.
doi:10.1016/S0924-977X(12)70269-9 .

Samardžić, Janko, Batinić, Bojan, Biawat, Poonam, Obradović, Dragan I., Cook, James M., Savić, Miroslav, "Acute effects of an inverse agonist selective for alpha(5) GABA(A) receptors on rat behaviour in the forced swim test" in European Neuropsychopharmacology, 22, no. Supplement 2 (2012):S187-S188,
https://doi.org/10.1016/S0924-977X(12)70269-9 . .