TY  - JOUR
AU  - Joksimović, Srđan
AU  - Divljaković, Jovana
AU  - van Linn, Michael
AU  - Varagić, Zdravko
AU  - Brajković, Gordana
AU  - Milinković, Marija M.
AU  - Yin, Wenyuan
AU  - Timić, Tamara
AU  - Sieghart, Werner
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2028
AB  - Despite significant advances in understanding the role of benzodiazepine (BZ)-sensitive populations of GABA A receptors, containing the α 1 , α 2 , α 3 or α 5 subunit, factual substrates of BZ-induced learning and memory deficits are not yet fully elucidated. It was shown that α 1 -subunit affinity-selective antagonist Β-CCt almost completely abolished spatial learning deficits induced by diazepam (DZP) in the Morris water maze. We examined a novel, highly (105 fold) α 1 -subunit selective ligand-WYS8 (0.2, 1 and 10mg/kg), on its own and in combination with the non-selective agonist DZP (2mg/kg) or Β-CCt (5mg/kg) in the water maze in rats. The in vitro efficacy study revealed that WYS8 acts as α 1 -subtype selective weak partial positive modulator (40% potentiation at 100nM). Measurement of concentrations of WYS8 and DZP in rat serum and brain tissues suggested that they did not substantially cross-influence the respective disposition. In the water maze, DZP impaired spatial learning (acquisition trials) and memory (probe trial). WYS8 caused no effect per se, did not affect the overall influence of DZP on the water-maze performance and was devoid of any activity in this task when combined with Β-CCt. Nonetheless, an additional analysis of the latency to reach the platform and the total distance swam suggested that WYS8 addition attenuated the run-down of the spatial impairment induced by DZP at the end of acquisition trials. These results demonstrate a clear difference in the influence of an α 1 subtype-selective antagonist and a partial agonist on the effects of DZP on the water-maze acquisition.
T2  - European Neuropsychopharmacology
T1  - Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors
VL  - 23
IS  - 5
SP  - 390
EP  - 399
DO  - 10.1016/j.euroneuro.2012.05.003
ER  - 

@article{
author = "Joksimović, Srđan and Divljaković, Jovana and van Linn, Michael and Varagić, Zdravko and Brajković, Gordana and Milinković, Marija M. and Yin, Wenyuan and Timić, Tamara and Sieghart, Werner and Cook, James M. and Savić, Miroslav",
year = "2013",
abstract = "Despite significant advances in understanding the role of benzodiazepine (BZ)-sensitive populations of GABA A receptors, containing the α 1 , α 2 , α 3 or α 5 subunit, factual substrates of BZ-induced learning and memory deficits are not yet fully elucidated. It was shown that α 1 -subunit affinity-selective antagonist Β-CCt almost completely abolished spatial learning deficits induced by diazepam (DZP) in the Morris water maze. We examined a novel, highly (105 fold) α 1 -subunit selective ligand-WYS8 (0.2, 1 and 10mg/kg), on its own and in combination with the non-selective agonist DZP (2mg/kg) or Β-CCt (5mg/kg) in the water maze in rats. The in vitro efficacy study revealed that WYS8 acts as α 1 -subtype selective weak partial positive modulator (40% potentiation at 100nM). Measurement of concentrations of WYS8 and DZP in rat serum and brain tissues suggested that they did not substantially cross-influence the respective disposition. In the water maze, DZP impaired spatial learning (acquisition trials) and memory (probe trial). WYS8 caused no effect per se, did not affect the overall influence of DZP on the water-maze performance and was devoid of any activity in this task when combined with Β-CCt. Nonetheless, an additional analysis of the latency to reach the platform and the total distance swam suggested that WYS8 addition attenuated the run-down of the spatial impairment induced by DZP at the end of acquisition trials. These results demonstrate a clear difference in the influence of an α 1 subtype-selective antagonist and a partial agonist on the effects of DZP on the water-maze acquisition.",
journal = "European Neuropsychopharmacology",
title = "Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors",
volume = "23",
number = "5",
pages = "390-399",
doi = "10.1016/j.euroneuro.2012.05.003"
}

Joksimović, S., Divljaković, J., van Linn, M., Varagić, Z., Brajković, G., Milinković, M. M., Yin, W., Timić, T., Sieghart, W., Cook, J. M.,& Savić, M.. (2013). Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors. in European Neuropsychopharmacology, 23(5), 390-399.
https://doi.org/10.1016/j.euroneuro.2012.05.003

Joksimović S, Divljaković J, van Linn M, Varagić Z, Brajković G, Milinković MM, Yin W, Timić T, Sieghart W, Cook JM, Savić M. Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors. in European Neuropsychopharmacology. 2013;23(5):390-399.
doi:10.1016/j.euroneuro.2012.05.003 .

Joksimović, Srđan, Divljaković, Jovana, van Linn, Michael, Varagić, Zdravko, Brajković, Gordana, Milinković, Marija M., Yin, Wenyuan, Timić, Tamara, Sieghart, Werner, Cook, James M., Savić, Miroslav, "Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptors" in European Neuropsychopharmacology, 23, no. 5 (2013):390-399,
https://doi.org/10.1016/j.euroneuro.2012.05.003 . .

TY  - JOUR
AU  - Joksimović, Srđan
AU  - Varagić, Zdravko
AU  - Kovacević, Jovana
AU  - van Linn, Michael
AU  - Milić, Marija
AU  - Rallapalli, Sundari
AU  - Timić, Tamara
AU  - Sieghart, Werner
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1839
AB  - Synthesis of ligands inactive or with low activity at alpha(1) GABA(A) receptors has become the key concept for development of novel, more tolerable benzodiazepine (BZ)-like drugs. WYS8, a remarkably (105 times) alpha(1)-subtype selective partial positive modulator, may serve as a pharmacological tool for refining the role of alpha(1) GABA(A) receptors in mediation of BZs' effects. Here, the effects of WYS8 on GABA-induced currents and on diazepam-induced potentiation of recombinant BZ-sensitive GABA(A) receptors were studied in more detail. In addition, the behavioral profile of WYS8 (0.2, 1, and 10 mg/kg i.p.), on its own and in combination with diazepam, was tested in the spontaneous locomotor activity, elevated plus maze, grip strength, rotarod, and pentylenetetrazole tests. WYS8, applied at an in vivo attainable concentration of 100 nM, reduced the stimulation of GABA currents by 1 mu M diazepam by 57 % at alpha(1)beta(3)gamma(2), but not at alpha(2)beta(3)gamma(2), alpha(3)beta(3)gamma(2), or alpha(5)beta(3)gamma(2) GABA(A) receptors. The administration of WYS8 alone induced negligible behavioral consequences. When combined with diazepam, WYS8 caused a reduction in sedation, muscle relaxation, and anticonvulsant activity, as compared with this BZ alone, whereas ataxia was preserved, and the anxiolytic effect of 2 mg/kg diazepam was unmasked. Hence, a partial instead of full activation at alpha(1) GABA(A) receptors did not necessarily result in the attenuation of the effects assumed to be mediated by activation of these receptors, or in the full preservation of the effects mediated by activation of other GABA(A) receptors. Thus, the role of alpha(1) GABA(A) receptors appears more complex than that proposed by genetic studies.
PB  - Springer, New York
T2  - QSAR & Combinatorial Science
T1  - Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?
VL  - 230
IS  - 1
SP  - 113
EP  - 123
DO  - 10.1007/s00213-013-3143-4
ER  - 

@article{
author = "Joksimović, Srđan and Varagić, Zdravko and Kovacević, Jovana and van Linn, Michael and Milić, Marija and Rallapalli, Sundari and Timić, Tamara and Sieghart, Werner and Cook, James M. and Savić, Miroslav",
year = "2013",
abstract = "Synthesis of ligands inactive or with low activity at alpha(1) GABA(A) receptors has become the key concept for development of novel, more tolerable benzodiazepine (BZ)-like drugs. WYS8, a remarkably (105 times) alpha(1)-subtype selective partial positive modulator, may serve as a pharmacological tool for refining the role of alpha(1) GABA(A) receptors in mediation of BZs' effects. Here, the effects of WYS8 on GABA-induced currents and on diazepam-induced potentiation of recombinant BZ-sensitive GABA(A) receptors were studied in more detail. In addition, the behavioral profile of WYS8 (0.2, 1, and 10 mg/kg i.p.), on its own and in combination with diazepam, was tested in the spontaneous locomotor activity, elevated plus maze, grip strength, rotarod, and pentylenetetrazole tests. WYS8, applied at an in vivo attainable concentration of 100 nM, reduced the stimulation of GABA currents by 1 mu M diazepam by 57 % at alpha(1)beta(3)gamma(2), but not at alpha(2)beta(3)gamma(2), alpha(3)beta(3)gamma(2), or alpha(5)beta(3)gamma(2) GABA(A) receptors. The administration of WYS8 alone induced negligible behavioral consequences. When combined with diazepam, WYS8 caused a reduction in sedation, muscle relaxation, and anticonvulsant activity, as compared with this BZ alone, whereas ataxia was preserved, and the anxiolytic effect of 2 mg/kg diazepam was unmasked. Hence, a partial instead of full activation at alpha(1) GABA(A) receptors did not necessarily result in the attenuation of the effects assumed to be mediated by activation of these receptors, or in the full preservation of the effects mediated by activation of other GABA(A) receptors. Thus, the role of alpha(1) GABA(A) receptors appears more complex than that proposed by genetic studies.",
publisher = "Springer, New York",
journal = "QSAR & Combinatorial Science",
title = "Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?",
volume = "230",
number = "1",
pages = "113-123",
doi = "10.1007/s00213-013-3143-4"
}

Joksimović, S., Varagić, Z., Kovacević, J., van Linn, M., Milić, M., Rallapalli, S., Timić, T., Sieghart, W., Cook, J. M.,& Savić, M.. (2013). Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?. in QSAR & Combinatorial Science
Springer, New York., 230(1), 113-123.
https://doi.org/10.1007/s00213-013-3143-4

Joksimović S, Varagić Z, Kovacević J, van Linn M, Milić M, Rallapalli S, Timić T, Sieghart W, Cook JM, Savić M. Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?. in QSAR & Combinatorial Science. 2013;230(1):113-123.
doi:10.1007/s00213-013-3143-4 .

Joksimović, Srđan, Varagić, Zdravko, Kovacević, Jovana, van Linn, Michael, Milić, Marija, Rallapalli, Sundari, Timić, Tamara, Sieghart, Werner, Cook, James M., Savić, Miroslav, "Insights into functional pharmacology of alpha(1) GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?" in QSAR & Combinatorial Science, 230, no. 1 (2013):113-123,
https://doi.org/10.1007/s00213-013-3143-4 . .

TY  - CONF
AU  - Divljaković, Jovana
AU  - Timić, Tamara
AU  - Milinković, Marija M.
AU  - Batinić, Bojan
AU  - van Linn, Michael
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1661
AB  - Objective : Despite a half century of clinical use and the recognized
potential of benzodiazepine dependence, the mechanisms under-
lying benzodiazepine withdrawal remain insufficiently understood.
The aim of the present study was to assess the influence of the non-
selective antagonist (flumazenil) and the preferential a1-subunit
selective antagonist (bCCt) on the anxiety level after diazepam with-
drawal.
Methods : The male Wistar rats were protractedly treated during
21 days with diazepam (2 mg/kg) or solvent. On the testing day,
24 hours after the last injection, animals from the diazepam-treated
groups received either antagonist (flumazenil or bCCt) or solvent, and
animals from the solvent-treated groups received solvent or diaze-
pam. Twenty minutes after administration of treatment on the testing
day, single animals were placed in the elevated plus maze in order to
assess the level of anxiety.
Results : Two-way ANOVA revealed that animals withdrawn from
diazepam spent significantly less time on the open arms than control
animals (p=0.023). One-way ANOVA, followed by post hoc test, re-
vealed that administration of flumazenil (10 mg/kg) or bCCt (1.25,
5 or 20 mg/kg) reversed the diazepam withdrawal-induced anxiety
(percentage of open arm time : p=0.003, p=0.032, p=0.031 and
p=0.014 compared to the diazepam-withdrawn group, respectively).
Concomitant administration of antagonists (10 mg/kg flumazenil,
or 1.25, 5 or 20 mg/kg bCCt) induced an anxiolytic effect comparable
to that observed after acutely administrated diazepam (percentage of
open arm time : p=0.142, p=0.187, p=0.243 and p=0.290, respect-
ively).
Conclusion : The present study demonstrated that administration
of the a1-selective antagonist bCCt or non-selective antagonist
flumazenil could prevent the withdrawal-induced anxiety and also
induce an anxiolytic-like effect. Moreover, presented results have
suggested that mechanism of preventing the withdrawal-induced
anxiety involves the antagonism at a1-containing GABAA receptors.
PB  - Oxford Univ Press, Oxford
C3  - International Journal of Neuropsychopharmacology
T1  - Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats
VL  - 15
IS  - Supplement 1
SP  - 201
EP  - 201
DO  - 10.1017/S1461145712000508
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1661
ER  - 

@conference{
author = "Divljaković, Jovana and Timić, Tamara and Milinković, Marija M. and Batinić, Bojan and van Linn, Michael and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Objective : Despite a half century of clinical use and the recognized
potential of benzodiazepine dependence, the mechanisms under-
lying benzodiazepine withdrawal remain insufficiently understood.
The aim of the present study was to assess the influence of the non-
selective antagonist (flumazenil) and the preferential a1-subunit
selective antagonist (bCCt) on the anxiety level after diazepam with-
drawal.
Methods : The male Wistar rats were protractedly treated during
21 days with diazepam (2 mg/kg) or solvent. On the testing day,
24 hours after the last injection, animals from the diazepam-treated
groups received either antagonist (flumazenil or bCCt) or solvent, and
animals from the solvent-treated groups received solvent or diaze-
pam. Twenty minutes after administration of treatment on the testing
day, single animals were placed in the elevated plus maze in order to
assess the level of anxiety.
Results : Two-way ANOVA revealed that animals withdrawn from
diazepam spent significantly less time on the open arms than control
animals (p=0.023). One-way ANOVA, followed by post hoc test, re-
vealed that administration of flumazenil (10 mg/kg) or bCCt (1.25,
5 or 20 mg/kg) reversed the diazepam withdrawal-induced anxiety
(percentage of open arm time : p=0.003, p=0.032, p=0.031 and
p=0.014 compared to the diazepam-withdrawn group, respectively).
Concomitant administration of antagonists (10 mg/kg flumazenil,
or 1.25, 5 or 20 mg/kg bCCt) induced an anxiolytic effect comparable
to that observed after acutely administrated diazepam (percentage of
open arm time : p=0.142, p=0.187, p=0.243 and p=0.290, respect-
ively).
Conclusion : The present study demonstrated that administration
of the a1-selective antagonist bCCt or non-selective antagonist
flumazenil could prevent the withdrawal-induced anxiety and also
induce an anxiolytic-like effect. Moreover, presented results have
suggested that mechanism of preventing the withdrawal-induced
anxiety involves the antagonism at a1-containing GABAA receptors.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Journal of Neuropsychopharmacology",
title = "Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats",
volume = "15",
number = "Supplement 1",
pages = "201-201",
doi = "10.1017/S1461145712000508",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1661"
}

Divljaković, J., Timić, T., Milinković, M. M., Batinić, B., van Linn, M., Cook, J. M.,& Savić, M.. (2012). Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats. in International Journal of Neuropsychopharmacology
Oxford Univ Press, Oxford., 15(Supplement 1), 201-201.
https://doi.org/10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1661

Divljaković J, Timić T, Milinković MM, Batinić B, van Linn M, Cook JM, Savić M. Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats. in International Journal of Neuropsychopharmacology. 2012;15(Supplement 1):201-201.
doi:10.1017/S1461145712000508
https://hdl.handle.net/21.15107/rcub_farfar_1661 .

Divljaković, Jovana, Timić, Tamara, Milinković, Marija M., Batinić, Bojan, van Linn, Michael, Cook, James M., Savić, Miroslav, "Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats" in International Journal of Neuropsychopharmacology, 15, no. Supplement 1 (2012):201-201,
https://doi.org/10.1017/S1461145712000508 .,
https://hdl.handle.net/21.15107/rcub_farfar_1661 .

TY  - JOUR
AU  - Milić, Marija
AU  - Divljaković, Jovana
AU  - Rallapalli, Sundari
AU  - van Linn, Michael
AU  - Timić, Tamara
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1698
AB  - Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of gamma-aminobutyric acid A (GABA(A)) receptors containing alpha(1) and alpha(5) subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the alpha(1)-selective agonist zolpidem, as well as nonselective, alpha(1)-subunit and alpha(5)-subunit-selective antagonists flumazenil, beta CCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10mg/kg) and beta CCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg/kg) significantly decreased the grip strength. These effects of zolpidem were reversed by beta CCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that alpha(1) GABA(A) receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas alpha(5) GABA(A) receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia. Behavioural Pharmacology 23:191-197
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Behavioural Pharmacology
T1  - The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats
VL  - 23
IS  - 2
SP  - 191
EP  - 197
DO  - 10.1097/FBP.0b013e3283512c85
ER  - 

@article{
author = "Milić, Marija and Divljaković, Jovana and Rallapalli, Sundari and van Linn, Michael and Timić, Tamara and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of gamma-aminobutyric acid A (GABA(A)) receptors containing alpha(1) and alpha(5) subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the alpha(1)-selective agonist zolpidem, as well as nonselective, alpha(1)-subunit and alpha(5)-subunit-selective antagonists flumazenil, beta CCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10mg/kg) and beta CCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg/kg) significantly decreased the grip strength. These effects of zolpidem were reversed by beta CCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that alpha(1) GABA(A) receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas alpha(5) GABA(A) receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia. Behavioural Pharmacology 23:191-197",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Behavioural Pharmacology",
title = "The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats",
volume = "23",
number = "2",
pages = "191-197",
doi = "10.1097/FBP.0b013e3283512c85"
}

Milić, M., Divljaković, J., Rallapalli, S., van Linn, M., Timić, T., Cook, J. M.,& Savić, M.. (2012). The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats. in Behavioural Pharmacology
Lippincott Williams & Wilkins, Philadelphia., 23(2), 191-197.
https://doi.org/10.1097/FBP.0b013e3283512c85

Milić M, Divljaković J, Rallapalli S, van Linn M, Timić T, Cook JM, Savić M. The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats. in Behavioural Pharmacology. 2012;23(2):191-197.
doi:10.1097/FBP.0b013e3283512c85 .

Milić, Marija, Divljaković, Jovana, Rallapalli, Sundari, van Linn, Michael, Timić, Tamara, Cook, James M., Savić, Miroslav, "The role of alpha(1) and alpha(5) subunit-containing GABA(A) receptors in motor impairment induced by benzodiazepines in rats" in Behavioural Pharmacology, 23, no. 2 (2012):191-197,
https://doi.org/10.1097/FBP.0b013e3283512c85 . .

TY  - JOUR
AU  - Savić, Miroslav
AU  - Kukić-Marković, Jelena
AU  - Grayer, Renee J.
AU  - Milinković, Marija M.
AU  - Marin, Petar
AU  - Divljaković, Jovana
AU  - van Linn, Michael
AU  - Cook, James M.
AU  - Petrović, Silvana
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1336
AB  - We performed a basic behavioral characterization of methanol extracts of four Balkan endemic Stachys taxa: S. anisochila (SA), S. beckeana (SB), S. plumosa (SP) and S. alpina subsp. dinarica (SAD). The behavioral activity of extracts dosed intraperitoneally in the range 100-400 mg/kg was examined in adult male Wistar rats, in the elevated plus maze, spontaneous locomotor activity, and grip strength tests, mainly predictive of anxiolytic, sedative and myorelaxant actions, respectively. All investigated Stachys extracts lacked anxiolytic or myorelaxant activities, while SB at 400 mg/kg exerted an anxiogenic-like effect. The study with the selective antagonist beta-CCt showed that the sedative effect of SAD was only partially mediated by GABAA receptors containing the alpha 1-subunit. While discernible, the behavioral effects of SA and SP were not distinct. In all extracts, chlorogenic acid and verbascoside were identified. In SA, SB, and SAD the flavonoid fraction was constituted of isoscutellarein and hypolaetine glycosides, while in SP chrysoeriol and apigenin glycosides were present. The results reveal the psychotropic potential of four endemic Stachys taxa, of which SAD appeared most promising as a natural sedative. Copyright
PB  - Wiley-Blackwell, Malden
T2  - Phytotherapy Research
T1  - Behavioural Characterization of Four Endemic Stachys Taxa
VL  - 24
IS  - 9
SP  - 1309
EP  - 1316
DO  - 10.1002/ptr.3106
ER  - 

@article{
author = "Savić, Miroslav and Kukić-Marković, Jelena and Grayer, Renee J. and Milinković, Marija M. and Marin, Petar and Divljaković, Jovana and van Linn, Michael and Cook, James M. and Petrović, Silvana",
year = "2010",
abstract = "We performed a basic behavioral characterization of methanol extracts of four Balkan endemic Stachys taxa: S. anisochila (SA), S. beckeana (SB), S. plumosa (SP) and S. alpina subsp. dinarica (SAD). The behavioral activity of extracts dosed intraperitoneally in the range 100-400 mg/kg was examined in adult male Wistar rats, in the elevated plus maze, spontaneous locomotor activity, and grip strength tests, mainly predictive of anxiolytic, sedative and myorelaxant actions, respectively. All investigated Stachys extracts lacked anxiolytic or myorelaxant activities, while SB at 400 mg/kg exerted an anxiogenic-like effect. The study with the selective antagonist beta-CCt showed that the sedative effect of SAD was only partially mediated by GABAA receptors containing the alpha 1-subunit. While discernible, the behavioral effects of SA and SP were not distinct. In all extracts, chlorogenic acid and verbascoside were identified. In SA, SB, and SAD the flavonoid fraction was constituted of isoscutellarein and hypolaetine glycosides, while in SP chrysoeriol and apigenin glycosides were present. The results reveal the psychotropic potential of four endemic Stachys taxa, of which SAD appeared most promising as a natural sedative. Copyright",
publisher = "Wiley-Blackwell, Malden",
journal = "Phytotherapy Research",
title = "Behavioural Characterization of Four Endemic Stachys Taxa",
volume = "24",
number = "9",
pages = "1309-1316",
doi = "10.1002/ptr.3106"
}

Savić, M., Kukić-Marković, J., Grayer, R. J., Milinković, M. M., Marin, P., Divljaković, J., van Linn, M., Cook, J. M.,& Petrović, S.. (2010). Behavioural Characterization of Four Endemic Stachys Taxa. in Phytotherapy Research
Wiley-Blackwell, Malden., 24(9), 1309-1316.
https://doi.org/10.1002/ptr.3106

Savić M, Kukić-Marković J, Grayer RJ, Milinković MM, Marin P, Divljaković J, van Linn M, Cook JM, Petrović S. Behavioural Characterization of Four Endemic Stachys Taxa. in Phytotherapy Research. 2010;24(9):1309-1316.
doi:10.1002/ptr.3106 .

Savić, Miroslav, Kukić-Marković, Jelena, Grayer, Renee J., Milinković, Marija M., Marin, Petar, Divljaković, Jovana, van Linn, Michael, Cook, James M., Petrović, Silvana, "Behavioural Characterization of Four Endemic Stachys Taxa" in Phytotherapy Research, 24, no. 9 (2010):1309-1316,
https://doi.org/10.1002/ptr.3106 . .

TY  - CONF
AU  - Divljaković, Jovana
AU  - van Linn, Michael
AU  - Milinković, Marija M.
AU  - Yin, Wenyuan
AU  - Batinić, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1352
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment
VL  - 20
IS  - Supplement 3
SP  - S261
EP  - S262
DO  - 10.1016/S0924-977X(10)70334-5
ER  - 

@conference{
author = "Divljaković, Jovana and van Linn, Michael and Milinković, Marija M. and Yin, Wenyuan and Batinić, Bojan and Cook, James M. and Savić, Miroslav",
year = "2010",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment",
volume = "20",
number = "Supplement 3",
pages = "S261-S262",
doi = "10.1016/S0924-977X(10)70334-5"
}

Divljaković, J., van Linn, M., Milinković, M. M., Yin, W., Batinić, B., Cook, J. M.,& Savić, M.. (2010). Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 20(Supplement 3), S261-S262.
https://doi.org/10.1016/S0924-977X(10)70334-5

Divljaković J, van Linn M, Milinković MM, Yin W, Batinić B, Cook JM, Savić M. Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment. in European Neuropsychopharmacology. 2010;20(Supplement 3):S261-S262.
doi:10.1016/S0924-977X(10)70334-5 .

Divljaković, Jovana, van Linn, Michael, Milinković, Marija M., Yin, Wenyuan, Batinić, Bojan, Cook, James M., Savić, Miroslav, "Contribution of a1 subunit-containing GABA-A receptors to diazepam-induced motor impairment" in European Neuropsychopharmacology, 20, no. Supplement 3 (2010):S261-S262,
https://doi.org/10.1016/S0924-977X(10)70334-5 . .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Savić, Miroslav
AU  - Milinković, Marija M.
AU  - van Linn, Michael
AU  - Ramerstorfer, Joachim
AU  - Majumder, Samarpan
AU  - Yin, Wenyuan
AU  - Roth, Brian L.
AU  - Sieghart, Werner
AU  - Cook, James M.
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1172
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?
VL  - 19
IS  - Supplement 3
SP  - S297
EP  - S297
DO  - 10.1016/S0924-977X(09)70440-7
ER  - 

@conference{
author = "Joksimović, Srđan and Savić, Miroslav and Milinković, Marija M. and van Linn, Michael and Ramerstorfer, Joachim and Majumder, Samarpan and Yin, Wenyuan and Roth, Brian L. and Sieghart, Werner and Cook, James M.",
year = "2009",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?",
volume = "19",
number = "Supplement 3",
pages = "S297-S297",
doi = "10.1016/S0924-977X(09)70440-7"
}

Joksimović, S., Savić, M., Milinković, M. M., van Linn, M., Ramerstorfer, J., Majumder, S., Yin, W., Roth, B. L., Sieghart, W.,& Cook, J. M.. (2009). WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 19(Supplement 3), S297-S297.
https://doi.org/10.1016/S0924-977X(09)70440-7

Joksimović S, Savić M, Milinković MM, van Linn M, Ramerstorfer J, Majumder S, Yin W, Roth BL, Sieghart W, Cook JM. WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?. in European Neuropsychopharmacology. 2009;19(Supplement 3):S297-S297.
doi:10.1016/S0924-977X(09)70440-7 .

Joksimović, Srđan, Savić, Miroslav, Milinković, Marija M., van Linn, Michael, Ramerstorfer, Joachim, Majumder, Samarpan, Yin, Wenyuan, Roth, Brian L., Sieghart, Werner, Cook, James M., "WYS-8, a novel ligand at GABAA receptors: a step forward to linking in vitro with in vivo selectivity?" in European Neuropsychopharmacology, 19, no. Supplement 3 (2009):S297-S297,
https://doi.org/10.1016/S0924-977X(09)70440-7 . .

TY  - JOUR
AU  - Savić, Miroslav
AU  - Milinković, Marija M.
AU  - Rallapalli, Sundari
AU  - Clayton, Terry
AU  - Joksimović, Srđan
AU  - van Linn, Michael
AU  - Cook, James M.
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1176
AB  - The clinical use of benzodiazepines (BZs) is hampered by sedation and cognitive deterioration. Although genetic and pharmacological studies suggest that alpha(1)- and alpha(5)-containing GABA(A) receptors mediate and/or modulate these effects, their molecular substrate is not fully elucidated. By the use of two selective ligands: the alpha(1)-subunit affinity-selective antagonist beta-CCt, and the alpha(5)-subunit affinity- and efficacy-selective antagonist XLi093, we examined the mechanisms of behavioural effects of diazepam in the tests of spontaneous locomotor activity and water-maze acquisition and recall, the two paradigms indicative of sedative- and cognition-impairing effects of BZs, respectively. The locomotor-activity decreasing propensity of diazepam (significant at 1.5 and 5 mg/kg) was antagonized by beta-CCt (5 and 15 mg/kg), while it tended to be potentiated by XLi093 in doses of 10 mg/kg, and especially 20 mg/kg. Diazepam decreased acquisition and recall in the water maze, with a minimum effective dose of 1.5 mg/kg. Both antagonists reversed the thigmotaxis induced by 2 mg/kg diazepam throughout the test, suggesting that both GABA(A) receptor subtypes participate in BZ effects on the procedural component of the task. Diazepam-induced impairment in the declarative component of the task, as assessed by path efficiency, the latency and distance before finding the platform across acquisition trials, and also by the spatial parameters in the probe trial, was partially prevented by both, 15 mg/kg beta-CCt and 10 mg/kg XLi093. Combining a BZ with beta-CCt results in the near to control level of performance of a cognitive task, without sedation, and may be worth testing on human subjects.
PB  - Oxford Univ Press, Oxford
T2  - International Journal of Neuropsychopharmacology
T1  - The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats
VL  - 12
IS  - 9
SP  - 1179
EP  - 1193
DO  - 10.1017/S1461145709000108
ER  - 

@article{
author = "Savić, Miroslav and Milinković, Marija M. and Rallapalli, Sundari and Clayton, Terry and Joksimović, Srđan and van Linn, Michael and Cook, James M.",
year = "2009",
abstract = "The clinical use of benzodiazepines (BZs) is hampered by sedation and cognitive deterioration. Although genetic and pharmacological studies suggest that alpha(1)- and alpha(5)-containing GABA(A) receptors mediate and/or modulate these effects, their molecular substrate is not fully elucidated. By the use of two selective ligands: the alpha(1)-subunit affinity-selective antagonist beta-CCt, and the alpha(5)-subunit affinity- and efficacy-selective antagonist XLi093, we examined the mechanisms of behavioural effects of diazepam in the tests of spontaneous locomotor activity and water-maze acquisition and recall, the two paradigms indicative of sedative- and cognition-impairing effects of BZs, respectively. The locomotor-activity decreasing propensity of diazepam (significant at 1.5 and 5 mg/kg) was antagonized by beta-CCt (5 and 15 mg/kg), while it tended to be potentiated by XLi093 in doses of 10 mg/kg, and especially 20 mg/kg. Diazepam decreased acquisition and recall in the water maze, with a minimum effective dose of 1.5 mg/kg. Both antagonists reversed the thigmotaxis induced by 2 mg/kg diazepam throughout the test, suggesting that both GABA(A) receptor subtypes participate in BZ effects on the procedural component of the task. Diazepam-induced impairment in the declarative component of the task, as assessed by path efficiency, the latency and distance before finding the platform across acquisition trials, and also by the spatial parameters in the probe trial, was partially prevented by both, 15 mg/kg beta-CCt and 10 mg/kg XLi093. Combining a BZ with beta-CCt results in the near to control level of performance of a cognitive task, without sedation, and may be worth testing on human subjects.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Journal of Neuropsychopharmacology",
title = "The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats",
volume = "12",
number = "9",
pages = "1179-1193",
doi = "10.1017/S1461145709000108"
}

Savić, M., Milinković, M. M., Rallapalli, S., Clayton, T., Joksimović, S., van Linn, M.,& Cook, J. M.. (2009). The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats. in International Journal of Neuropsychopharmacology
Oxford Univ Press, Oxford., 12(9), 1179-1193.
https://doi.org/10.1017/S1461145709000108

Savić M, Milinković MM, Rallapalli S, Clayton T, Joksimović S, van Linn M, Cook JM. The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats. in International Journal of Neuropsychopharmacology. 2009;12(9):1179-1193.
doi:10.1017/S1461145709000108 .

Savić, Miroslav, Milinković, Marija M., Rallapalli, Sundari, Clayton, Terry, Joksimović, Srđan, van Linn, Michael, Cook, James M., "The differential role of alpha(1)- and alpha(5)-containing GABA(A) receptors in mediating diazepam effects on spontaneous locomotor activity and water-maze learning and memory in rats" in International Journal of Neuropsychopharmacology, 12, no. 9 (2009):1179-1193,
https://doi.org/10.1017/S1461145709000108 . .

TY  - CONF
AU  - Joksimović, Srđan
AU  - Savić, Miroslav
AU  - Clayton, Terry
AU  - Huang, Shengming
AU  - Ara, S.
AU  - van Linn, Michael
AU  - Milinković, Marija M.
AU  - Bokonjić, Dubravko
AU  - Sieghart, Werner
AU  - Cook, James M.
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1079
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze
VL  - 18
IS  - Supplement 4
SP  - S282
EP  - S282
DO  - 10.1016/S0924-977X(08)70372-9
ER  - 

@conference{
author = "Joksimović, Srđan and Savić, Miroslav and Clayton, Terry and Huang, Shengming and Ara, S. and van Linn, Michael and Milinković, Marija M. and Bokonjić, Dubravko and Sieghart, Werner and Cook, James M.",
year = "2008",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze",
volume = "18",
number = "Supplement 4",
pages = "S282-S282",
doi = "10.1016/S0924-977X(08)70372-9"
}

Joksimović, S., Savić, M., Clayton, T., Huang, S., Ara, S., van Linn, M., Milinković, M. M., Bokonjić, D., Sieghart, W.,& Cook, J. M.. (2008). Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 18(Supplement 4), S282-S282.
https://doi.org/10.1016/S0924-977X(08)70372-9

Joksimović S, Savić M, Clayton T, Huang S, Ara S, van Linn M, Milinković MM, Bokonjić D, Sieghart W, Cook JM. Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze. in European Neuropsychopharmacology. 2008;18(Supplement 4):S282-S282.
doi:10.1016/S0924-977X(08)70372-9 .

Joksimović, Srđan, Savić, Miroslav, Clayton, Terry, Huang, Shengming, Ara, S., van Linn, Michael, Milinković, Marija M., Bokonjić, Dubravko, Sieghart, Werner, Cook, James M., "Relative contribution of the alpha2-, 3-and 5-containing GABAA receptors to benzodiazepine effects in the water maze" in European Neuropsychopharmacology, 18, no. Supplement 4 (2008):S282-S282,
https://doi.org/10.1016/S0924-977X(08)70372-9 . .

TY  - CONF
AU  - Milinković, Marija M.
AU  - Savić, Miroslav
AU  - Rallapalli, Sundari
AU  - Samardžić, Janko
AU  - van Linn, Michael
AU  - Ugrešić, Nenad
AU  - Cook, James M.
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1063
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - RY-023, an inverse agonist at alpha5 GABAA receptors: the influence on spatial memory and spontaneous locomotor activity
VL  - 18
IS  - Supplement 4
SP  - S284
EP  - S284
DO  - 10.1016/S0924-977X(08)70375-4
ER  - 

@conference{
author = "Milinković, Marija M. and Savić, Miroslav and Rallapalli, Sundari and Samardžić, Janko and van Linn, Michael and Ugrešić, Nenad and Cook, James M.",
year = "2008",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "RY-023, an inverse agonist at alpha5 GABAA receptors: the influence on spatial memory and spontaneous locomotor activity",
volume = "18",
number = "Supplement 4",
pages = "S284-S284",
doi = "10.1016/S0924-977X(08)70375-4"
}

Milinković, M. M., Savić, M., Rallapalli, S., Samardžić, J., van Linn, M., Ugrešić, N.,& Cook, J. M.. (2008). RY-023, an inverse agonist at alpha5 GABAA receptors: the influence on spatial memory and spontaneous locomotor activity. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 18(Supplement 4), S284-S284.
https://doi.org/10.1016/S0924-977X(08)70375-4

Milinković MM, Savić M, Rallapalli S, Samardžić J, van Linn M, Ugrešić N, Cook JM. RY-023, an inverse agonist at alpha5 GABAA receptors: the influence on spatial memory and spontaneous locomotor activity. in European Neuropsychopharmacology. 2008;18(Supplement 4):S284-S284.
doi:10.1016/S0924-977X(08)70375-4 .

Milinković, Marija M., Savić, Miroslav, Rallapalli, Sundari, Samardžić, Janko, van Linn, Michael, Ugrešić, Nenad, Cook, James M., "RY-023, an inverse agonist at alpha5 GABAA receptors: the influence on spatial memory and spontaneous locomotor activity" in European Neuropsychopharmacology, 18, no. Supplement 4 (2008):S284-S284,
https://doi.org/10.1016/S0924-977X(08)70375-4 . .

TY  - CONF
AU  - Savić, Miroslav
AU  - Rallapalli, Sundari
AU  - Milinković, Marija M.
AU  - Samardžić, Janko
AU  - van Linn, Michael
AU  - Cook, James M.
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1102
PB  - Cambridge Univ Press, New York
C3  - International Journal of Neuropsychopharmacology
T1  - Hypolocomotor activity of DIAZEPAM in wistar rats is mediated by Gabaa receptors containing the Alphal, but not the Alpha5 subunit
VL  - 11
SP  - 212
EP  - 212
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1102
ER  - 

@conference{
author = "Savić, Miroslav and Rallapalli, Sundari and Milinković, Marija M. and Samardžić, Janko and van Linn, Michael and Cook, James M.",
year = "2008",
publisher = "Cambridge Univ Press, New York",
journal = "International Journal of Neuropsychopharmacology",
title = "Hypolocomotor activity of DIAZEPAM in wistar rats is mediated by Gabaa receptors containing the Alphal, but not the Alpha5 subunit",
volume = "11",
pages = "212-212",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1102"
}

Savić, M., Rallapalli, S., Milinković, M. M., Samardžić, J., van Linn, M.,& Cook, J. M.. (2008). Hypolocomotor activity of DIAZEPAM in wistar rats is mediated by Gabaa receptors containing the Alphal, but not the Alpha5 subunit. in International Journal of Neuropsychopharmacology
Cambridge Univ Press, New York., 11, 212-212.
https://hdl.handle.net/21.15107/rcub_farfar_1102

Savić M, Rallapalli S, Milinković MM, Samardžić J, van Linn M, Cook JM. Hypolocomotor activity of DIAZEPAM in wistar rats is mediated by Gabaa receptors containing the Alphal, but not the Alpha5 subunit. in International Journal of Neuropsychopharmacology. 2008;11:212-212.
https://hdl.handle.net/21.15107/rcub_farfar_1102 .

Savić, Miroslav, Rallapalli, Sundari, Milinković, Marija M., Samardžić, Janko, van Linn, Michael, Cook, James M., "Hypolocomotor activity of DIAZEPAM in wistar rats is mediated by Gabaa receptors containing the Alphal, but not the Alpha5 subunit" in International Journal of Neuropsychopharmacology, 11 (2008):212-212,
https://hdl.handle.net/21.15107/rcub_farfar_1102 .

TY  - CONF
AU  - Cook, James M.
AU  - June, Harry
AU  - Weerts, Elise
AU  - van Linn, Michael
AU  - Platt, Donna
AU  - DeLorey, Tim
AU  - Savić, Miroslav
AU  - Clayton, Terry
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/949
PB  - Amer Chemical Soc, Washington
C3  - Abstracts of Papers of the American Chemical Society
T1  - MEDI 208-Serendipity rediscovered u an oxymoron or rational drug design: Studies on subtype selective BzR/GABAergic ligands
VL  - 234
UR  - https://hdl.handle.net/21.15107/rcub_farfar_949
ER  - 

@conference{
author = "Cook, James M. and June, Harry and Weerts, Elise and van Linn, Michael and Platt, Donna and DeLorey, Tim and Savić, Miroslav and Clayton, Terry",
year = "2007",
publisher = "Amer Chemical Soc, Washington",
journal = "Abstracts of Papers of the American Chemical Society",
title = "MEDI 208-Serendipity rediscovered u an oxymoron or rational drug design: Studies on subtype selective BzR/GABAergic ligands",
volume = "234",
url = "https://hdl.handle.net/21.15107/rcub_farfar_949"
}

Cook, J. M., June, H., Weerts, E., van Linn, M., Platt, D., DeLorey, T., Savić, M.,& Clayton, T.. (2007). MEDI 208-Serendipity rediscovered u an oxymoron or rational drug design: Studies on subtype selective BzR/GABAergic ligands. in Abstracts of Papers of the American Chemical Society
Amer Chemical Soc, Washington., 234.
https://hdl.handle.net/21.15107/rcub_farfar_949

Cook JM, June H, Weerts E, van Linn M, Platt D, DeLorey T, Savić M, Clayton T. MEDI 208-Serendipity rediscovered u an oxymoron or rational drug design: Studies on subtype selective BzR/GABAergic ligands. in Abstracts of Papers of the American Chemical Society. 2007;234.
https://hdl.handle.net/21.15107/rcub_farfar_949 .

Cook, James M., June, Harry, Weerts, Elise, van Linn, Michael, Platt, Donna, DeLorey, Tim, Savić, Miroslav, Clayton, Terry, "MEDI 208-Serendipity rediscovered u an oxymoron or rational drug design: Studies on subtype selective BzR/GABAergic ligands" in Abstracts of Papers of the American Chemical Society, 234 (2007),
https://hdl.handle.net/21.15107/rcub_farfar_949 .

TY  - JOUR
AU  - Savić, Miroslav
AU  - Obradović, Dragan I.
AU  - Ugrešić, Nenad
AU  - Cook, James M.
AU  - Yin, Wenyuan
AU  - van Linn, Michael
AU  - Bokonjić, Dubravko
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/828
AB  - Benzodiazepine site inverse agonists may increase or decrease locomotor activity in rodents, depending on the experimental settings. We have compared the behavioral responses to environmental novelty of rats treated with the non-selective inverse agonist DMCM (2 mg/kg) and the alpha(1)-subunit affinity-selective inverse agonist 3-EBC (15 mg/kg). The behavior in spontaneous locomotor assay (during 45 min) and elevated plus maze (EPM) was automatically recorded. In the EPM, general activity-related parameters were similarly decreased, whereas only DMCM inhibited open-arm activity. In the locomotor assay, both compounds depressed locomotion in the first 15 min and activity in the central zone of the chamber. However, the influence of 3-EBC was less pronounced. The alpha(1)-subunit selective antagonist beta-CCt (15 mg/kg) attenuated locomotor depression, but not the central-zone avoidance elicited by DMCM. When habituated to the chamber, DMCM-treated animals emitted a plateau phase of activity, which disappeared by adding beta-CCt. Hence, inhibition of activity in exposed areas may be mediated by non-alpha(1)-subunits, whereas both alpha(1) and non-alpha(1)-subunits may participate in suppression of activity in more protective areas of an apparatus. Hyperlocomotion in habituated animals may depend primarily on the alpha(1)-subunit. Moreover, the bimodal influence of inverse agonists on locomotion can be biphasic, observable in the same experiment.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Pharmacology Biochemistry and Behavior
T1  - Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence
VL  - 84
IS  - 1
SP  - 35
EP  - 42
DO  - 10.1016/j.pbb.2006.04.001
ER  - 

@article{
author = "Savić, Miroslav and Obradović, Dragan I. and Ugrešić, Nenad and Cook, James M. and Yin, Wenyuan and van Linn, Michael and Bokonjić, Dubravko",
year = "2006",
abstract = "Benzodiazepine site inverse agonists may increase or decrease locomotor activity in rodents, depending on the experimental settings. We have compared the behavioral responses to environmental novelty of rats treated with the non-selective inverse agonist DMCM (2 mg/kg) and the alpha(1)-subunit affinity-selective inverse agonist 3-EBC (15 mg/kg). The behavior in spontaneous locomotor assay (during 45 min) and elevated plus maze (EPM) was automatically recorded. In the EPM, general activity-related parameters were similarly decreased, whereas only DMCM inhibited open-arm activity. In the locomotor assay, both compounds depressed locomotion in the first 15 min and activity in the central zone of the chamber. However, the influence of 3-EBC was less pronounced. The alpha(1)-subunit selective antagonist beta-CCt (15 mg/kg) attenuated locomotor depression, but not the central-zone avoidance elicited by DMCM. When habituated to the chamber, DMCM-treated animals emitted a plateau phase of activity, which disappeared by adding beta-CCt. Hence, inhibition of activity in exposed areas may be mediated by non-alpha(1)-subunits, whereas both alpha(1) and non-alpha(1)-subunits may participate in suppression of activity in more protective areas of an apparatus. Hyperlocomotion in habituated animals may depend primarily on the alpha(1)-subunit. Moreover, the bimodal influence of inverse agonists on locomotion can be biphasic, observable in the same experiment.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Pharmacology Biochemistry and Behavior",
title = "Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence",
volume = "84",
number = "1",
pages = "35-42",
doi = "10.1016/j.pbb.2006.04.001"
}

Savić, M., Obradović, D. I., Ugrešić, N., Cook, J. M., Yin, W., van Linn, M.,& Bokonjić, D.. (2006). Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence. in Pharmacology Biochemistry and Behavior
Pergamon-Elsevier Science Ltd, Oxford., 84(1), 35-42.
https://doi.org/10.1016/j.pbb.2006.04.001

Savić M, Obradović DI, Ugrešić N, Cook JM, Yin W, van Linn M, Bokonjić D. Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence. in Pharmacology Biochemistry and Behavior. 2006;84(1):35-42.
doi:10.1016/j.pbb.2006.04.001 .

Savić, Miroslav, Obradović, Dragan I., Ugrešić, Nenad, Cook, James M., Yin, Wenyuan, van Linn, Michael, Bokonjić, Dubravko, "Benzodiazepine site inverse agonists and locomotor activity in rats: Bimodal and biphasic influence" in Pharmacology Biochemistry and Behavior, 84, no. 1 (2006):35-42,
https://doi.org/10.1016/j.pbb.2006.04.001 . .