TY  - JOUR
AU  - Vasović, Dina
AU  - Divović, Branka
AU  - Treven, Marco
AU  - Knutson, Daniel
AU  - Steudle, Friederike
AU  - Scholze, Petra
AU  - Obradović, Aleksandar
AU  - Fabjan, Jure
AU  - Brković, Božidar
AU  - Sieghart, Werner
AU  - Ernst, Margot
AU  - Cook, James
AU  - Savić, Miroslav
PY  - 2019
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2384
AB  - gamma-Aminobutyric acid type A (GABA(A)) receptors containing the alpha 6 subunit are located in trigeminal ganglia, and their reduction by small interfering RNA increases inflammatory temporomandibular and myofascial pain in rats. We thus hypothesized that enhancing their activity may help in neuropathic syndromes originating from the trigeminal system. Here, we performed a detailed electrophysiological and pharmacokinetic analysis of two recently developed deuterated structurally similar pyrazoloquinolinone compounds. DK-I-56-1 at concentrations below 1 mu M enhanced gamma-aminobutyric acid (GABA) currents at recombinant rat alpha 6 beta 3 gamma 2, alpha 6 beta 3 delta and alpha 6 beta 3 receptors, whereas it was inactive at most GABA(A) receptor subtypes containing other alpha subunits. DK-I-87-1 at concentrations below 1 mu M was inactive at alpha 6-containing receptors and only weakly modulated other GABA(A) receptors investigated. Both plasma and brain tissue kinetics of DK-I-56-1 were relatively slow, with half-lives of 6 and 13 hr, respectively, enabling the persistence of estimated free brain concentrations in the range 10-300 nM throughout a 24-hr period. Results obtained in two protocols of chronic constriction injury of the infraorbital nerve in rats dosed intraperitoneally with DK-I-56-1 during 14 days after surgery or with DK-I-56-1 or DK-I-87-1 during 14 days after trigeminal neuropathy were already established, demonstrated that DK-I-56-1 but not DK-I-87-1 significantly reduced the hypersensitivity response to von Frey filaments. Significance Neuropathic pain induced by trigeminal nerve damage is poorly controlled by current treatments. DK-I-56-1 that positively modulates alpha 6 GABA(A) receptors is appropriate for repeated administration and thus may represent a novel treatment option against the development and maintenance of trigeminal neuropathic pain.
PB  - Wiley, Hoboken
T2  - European Journal of Pain
T1  - Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of alpha 6 GABA(A) receptors
VL  - 23
IS  - 5
SP  - 973
EP  - 984
DO  - 10.1002/ejp.1365
ER  - 

@article{
author = "Vasović, Dina and Divović, Branka and Treven, Marco and Knutson, Daniel and Steudle, Friederike and Scholze, Petra and Obradović, Aleksandar and Fabjan, Jure and Brković, Božidar and Sieghart, Werner and Ernst, Margot and Cook, James and Savić, Miroslav",
year = "2019",
abstract = "gamma-Aminobutyric acid type A (GABA(A)) receptors containing the alpha 6 subunit are located in trigeminal ganglia, and their reduction by small interfering RNA increases inflammatory temporomandibular and myofascial pain in rats. We thus hypothesized that enhancing their activity may help in neuropathic syndromes originating from the trigeminal system. Here, we performed a detailed electrophysiological and pharmacokinetic analysis of two recently developed deuterated structurally similar pyrazoloquinolinone compounds. DK-I-56-1 at concentrations below 1 mu M enhanced gamma-aminobutyric acid (GABA) currents at recombinant rat alpha 6 beta 3 gamma 2, alpha 6 beta 3 delta and alpha 6 beta 3 receptors, whereas it was inactive at most GABA(A) receptor subtypes containing other alpha subunits. DK-I-87-1 at concentrations below 1 mu M was inactive at alpha 6-containing receptors and only weakly modulated other GABA(A) receptors investigated. Both plasma and brain tissue kinetics of DK-I-56-1 were relatively slow, with half-lives of 6 and 13 hr, respectively, enabling the persistence of estimated free brain concentrations in the range 10-300 nM throughout a 24-hr period. Results obtained in two protocols of chronic constriction injury of the infraorbital nerve in rats dosed intraperitoneally with DK-I-56-1 during 14 days after surgery or with DK-I-56-1 or DK-I-87-1 during 14 days after trigeminal neuropathy were already established, demonstrated that DK-I-56-1 but not DK-I-87-1 significantly reduced the hypersensitivity response to von Frey filaments. Significance Neuropathic pain induced by trigeminal nerve damage is poorly controlled by current treatments. DK-I-56-1 that positively modulates alpha 6 GABA(A) receptors is appropriate for repeated administration and thus may represent a novel treatment option against the development and maintenance of trigeminal neuropathic pain.",
publisher = "Wiley, Hoboken",
journal = "European Journal of Pain",
title = "Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of alpha 6 GABA(A) receptors",
volume = "23",
number = "5",
pages = "973-984",
doi = "10.1002/ejp.1365"
}

Vasović, D., Divović, B., Treven, M., Knutson, D., Steudle, F., Scholze, P., Obradović, A., Fabjan, J., Brković, B., Sieghart, W., Ernst, M., Cook, J.,& Savić, M.. (2019). Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of alpha 6 GABA(A) receptors. in European Journal of Pain
Wiley, Hoboken., 23(5), 973-984.
https://doi.org/10.1002/ejp.1365

Vasović D, Divović B, Treven M, Knutson D, Steudle F, Scholze P, Obradović A, Fabjan J, Brković B, Sieghart W, Ernst M, Cook J, Savić M. Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of alpha 6 GABA(A) receptors. in European Journal of Pain. 2019;23(5):973-984.
doi:10.1002/ejp.1365 .

Vasović, Dina, Divović, Branka, Treven, Marco, Knutson, Daniel, Steudle, Friederike, Scholze, Petra, Obradović, Aleksandar, Fabjan, Jure, Brković, Božidar, Sieghart, Werner, Ernst, Margot, Cook, James, Savić, Miroslav, "Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of alpha 6 GABA(A) receptors" in European Journal of Pain, 23, no. 5 (2019):973-984,
https://doi.org/10.1002/ejp.1365 . .

TY  - CONF
AU  - Knutson, Daniel
AU  - Vasović, Dina
AU  - Divović, Branka
AU  - Treven, Marco
AU  - Steudle, Friederike
AU  - Scholze, Petra
AU  - Brković, Božidar
AU  - Sieghart, Werner
AU  - Ernst, Margot
AU  - Cook, James
AU  - Savić, Miroslav
PY  - 2018
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2316
PB  - Amer Chemical Soc, Washington
C3  - Abstracts of Papers of the American Chemical Society
T1  - Prevention of trigeminal neuropathic pain development in rats using novel deuterated GABAAR-alpha 6 subtype selective ligands
VL  - 256
UR  - https://hdl.handle.net/21.15107/rcub_smile_2316
ER  - 

@conference{
author = "Knutson, Daniel and Vasović, Dina and Divović, Branka and Treven, Marco and Steudle, Friederike and Scholze, Petra and Brković, Božidar and Sieghart, Werner and Ernst, Margot and Cook, James and Savić, Miroslav",
year = "2018",
publisher = "Amer Chemical Soc, Washington",
journal = "Abstracts of Papers of the American Chemical Society",
title = "Prevention of trigeminal neuropathic pain development in rats using novel deuterated GABAAR-alpha 6 subtype selective ligands",
volume = "256",
url = "https://hdl.handle.net/21.15107/rcub_smile_2316"
}

Knutson, D., Vasović, D., Divović, B., Treven, M., Steudle, F., Scholze, P., Brković, B., Sieghart, W., Ernst, M., Cook, J.,& Savić, M.. (2018). Prevention of trigeminal neuropathic pain development in rats using novel deuterated GABAAR-alpha 6 subtype selective ligands. in Abstracts of Papers of the American Chemical Society
Amer Chemical Soc, Washington., 256.
https://hdl.handle.net/21.15107/rcub_smile_2316

Knutson D, Vasović D, Divović B, Treven M, Steudle F, Scholze P, Brković B, Sieghart W, Ernst M, Cook J, Savić M. Prevention of trigeminal neuropathic pain development in rats using novel deuterated GABAAR-alpha 6 subtype selective ligands. in Abstracts of Papers of the American Chemical Society. 2018;256.
https://hdl.handle.net/21.15107/rcub_smile_2316 .

Knutson, Daniel, Vasović, Dina, Divović, Branka, Treven, Marco, Steudle, Friederike, Scholze, Petra, Brković, Božidar, Sieghart, Werner, Ernst, Margot, Cook, James, Savić, Miroslav, "Prevention of trigeminal neuropathic pain development in rats using novel deuterated GABAAR-alpha 6 subtype selective ligands" in Abstracts of Papers of the American Chemical Society, 256 (2018),
https://hdl.handle.net/21.15107/rcub_smile_2316 .

TY  - JOUR
AU  - Brković, Božidar
AU  - Savić, Miroslav
AU  - Andrić, Miroslav
AU  - Jurišić, Milan
AU  - Todorović, Ljubomir
PY  - 2010
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1565
AB  - There is no data concerning the use of the intraseptal anaesthesia (ISA) for single tooth extraction. The aims of this study were to compare the clinical efficacy and haemodynamic responses of the ISA with the periodontal ligament anaesthesia (PLA) for single tooth extraction. Thirty-five randomly selected healthy patients (ASA I) undergoing maxillary lateral incisors extraction entered the study. Onset of anaesthesia, the width of the anaesthetic field and duration of anaesthesia were recorded by pinprick testing. Intensity of anaesthesia was evaluated on a visual analogue scale. Haemodynamic parameters were recorded simultaneously at different time points after anaesthesia injection. The two techniques of local anaesthesia did not show statistically significant differences regarding the success rate and onset of anaesthesia, while the duration of the ISA on the buccal site was significantly longer in comparison with the PLA. The intensity of the achieved anaesthesia, estimated by the experienced pain during procedure, pointed out that pain was recorded in 24% of cases in the ISA group, and in 19% in the PLA group without significant differences. Postoperative pain was found to be smaller in the ISA group (70.9% of treated sites) than in the PLA group (81.3% of treated sites); however, this difference was not significant. Although the heart rate increased in both groups, there were no significant differences in the patients' haemodynamic response between the ISA and the PLA. The results of the present study indicate that both techniques are useful and suitable for the routine tooth extraction.
PB  - Springer Heidelberg, Heidelberg
T2  - Clinical Oral Investigations
T1  - Intraseptal vs. periodontal ligament anaesthesia for maxillary tooth extraction: quality of local anaesthesia and haemodynamic response
VL  - 14
IS  - 6
SP  - 675
EP  - 681
DO  - 10.1007/s00784-009-0352-7
ER  - 

@article{
author = "Brković, Božidar and Savić, Miroslav and Andrić, Miroslav and Jurišić, Milan and Todorović, Ljubomir",
year = "2010",
abstract = "There is no data concerning the use of the intraseptal anaesthesia (ISA) for single tooth extraction. The aims of this study were to compare the clinical efficacy and haemodynamic responses of the ISA with the periodontal ligament anaesthesia (PLA) for single tooth extraction. Thirty-five randomly selected healthy patients (ASA I) undergoing maxillary lateral incisors extraction entered the study. Onset of anaesthesia, the width of the anaesthetic field and duration of anaesthesia were recorded by pinprick testing. Intensity of anaesthesia was evaluated on a visual analogue scale. Haemodynamic parameters were recorded simultaneously at different time points after anaesthesia injection. The two techniques of local anaesthesia did not show statistically significant differences regarding the success rate and onset of anaesthesia, while the duration of the ISA on the buccal site was significantly longer in comparison with the PLA. The intensity of the achieved anaesthesia, estimated by the experienced pain during procedure, pointed out that pain was recorded in 24% of cases in the ISA group, and in 19% in the PLA group without significant differences. Postoperative pain was found to be smaller in the ISA group (70.9% of treated sites) than in the PLA group (81.3% of treated sites); however, this difference was not significant. Although the heart rate increased in both groups, there were no significant differences in the patients' haemodynamic response between the ISA and the PLA. The results of the present study indicate that both techniques are useful and suitable for the routine tooth extraction.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Clinical Oral Investigations",
title = "Intraseptal vs. periodontal ligament anaesthesia for maxillary tooth extraction: quality of local anaesthesia and haemodynamic response",
volume = "14",
number = "6",
pages = "675-681",
doi = "10.1007/s00784-009-0352-7"
}

Brković, B., Savić, M., Andrić, M., Jurišić, M.,& Todorović, L.. (2010). Intraseptal vs. periodontal ligament anaesthesia for maxillary tooth extraction: quality of local anaesthesia and haemodynamic response. in Clinical Oral Investigations
Springer Heidelberg, Heidelberg., 14(6), 675-681.
https://doi.org/10.1007/s00784-009-0352-7

Brković B, Savić M, Andrić M, Jurišić M, Todorović L. Intraseptal vs. periodontal ligament anaesthesia for maxillary tooth extraction: quality of local anaesthesia and haemodynamic response. in Clinical Oral Investigations. 2010;14(6):675-681.
doi:10.1007/s00784-009-0352-7 .

Brković, Božidar, Savić, Miroslav, Andrić, Miroslav, Jurišić, Milan, Todorović, Ljubomir, "Intraseptal vs. periodontal ligament anaesthesia for maxillary tooth extraction: quality of local anaesthesia and haemodynamic response" in Clinical Oral Investigations, 14, no. 6 (2010):675-681,
https://doi.org/10.1007/s00784-009-0352-7 . .

TY  - CONF
AU  - Savić, Miroslav
AU  - Brković, Božidar
AU  - Ugrešić, N.
PY  - 2006
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1302
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju
T1  - Nimesulide: Current safety profile
T1  - Nimesulid - aktuelni bezbednosni profil
VL  - 56
IS  - 4
SP  - 392
EP  - 393
UR  - https://hdl.handle.net/21.15107/rcub_smile_1302
ER  - 

@conference{
author = "Savić, Miroslav and Brković, Božidar and Ugrešić, N.",
year = "2006",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Nimesulide: Current safety profile, Nimesulid - aktuelni bezbednosni profil",
volume = "56",
number = "4",
pages = "392-393",
url = "https://hdl.handle.net/21.15107/rcub_smile_1302"
}

Savić, M., Brković, B.,& Ugrešić, N.. (2006). Nimesulide: Current safety profile. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 56(4), 392-393.
https://hdl.handle.net/21.15107/rcub_smile_1302

Savić M, Brković B, Ugrešić N. Nimesulide: Current safety profile. in Arhiv za farmaciju. 2006;56(4):392-393.
https://hdl.handle.net/21.15107/rcub_smile_1302 .

Savić, Miroslav, Brković, Božidar, Ugrešić, N., "Nimesulide: Current safety profile" in Arhiv za farmaciju, 56, no. 4 (2006):392-393,
https://hdl.handle.net/21.15107/rcub_smile_1302 .