TY  - JOUR
AU  - Divović-Matović, Branka
AU  - Knutson, Dan
AU  - Mitrović, Jelena
AU  - Stevanović, Vladimir
AU  - Stanojević, Boban
AU  - Savić, Snežana
AU  - Cook, James
AU  - Savić, Miroslav
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4289
AB  - Several pyrazoloquinolinone (PQ) ligands were recently discovered as func-tionally selective positive modulators at the PQ site ofα6-containing GABAAreceptors. PQs are also neutral modulators at the benzodiazepine site. Weassessed the influence of PQ compounds from three structural groups (PZ-II-029 and related deuterated analogues DK-I-56-1, RV-I-029, DK-I-60-3 and DK-I-86-1; LAU 463 and related analogues DK-I-58-1 and DK-II-58-1; and DK-I-87-1), alone and in combination with diazepam, on the behaviour of maleSprague–Dawley rats. An excellent behavioural safety profile of all tested PQswas demonstrated in the spontaneous locomotor activity, rotarod, loss of right-ing reflex and pentylenetetrazol tests. In interaction studies, only PZ-II-029and its analogues prevented the ataxic effects of the benzodiazepine, asassessed in the rotarod test and during monitoring of rat locomotor activityafter awakening from the loss of righting reflex. Published electrophysiologicalprofiles of PQ ligands imply that positive modulation elicited atα6-GABAAreceptors that contain theγ2 andδsubunit, rather than their neutral modula-tory action at the benzodiazepine site, may prevent the ataxic action of diaze-pam. Thus, PZ-II-029 and its deuterated analogues are not prone to untowardinteractions with benzodiazepines and may indeed completely abolish theirataxic action, seen at therapeutic, and especially toxic concentrations.
PB  - John Wiley and Sons Inc
T2  - Basic and Clinical Pharmacology and Toxicology
T1  - Behavioural interaction of pyrazoloquinolinone positive allosteric modulators at α6GABAA receptors and diazepam in rats: Anti-diazepam-induced ataxia action as a structure-dependent feature
VL  - 131
IS  - 6
SP  - 514
EP  - 524
DO  - 10.1111/bcpt.13801
ER  - 

@article{
author = "Divović-Matović, Branka and Knutson, Dan and Mitrović, Jelena and Stevanović, Vladimir and Stanojević, Boban and Savić, Snežana and Cook, James and Savić, Miroslav",
year = "2022",
abstract = "Several pyrazoloquinolinone (PQ) ligands were recently discovered as func-tionally selective positive modulators at the PQ site ofα6-containing GABAAreceptors. PQs are also neutral modulators at the benzodiazepine site. Weassessed the influence of PQ compounds from three structural groups (PZ-II-029 and related deuterated analogues DK-I-56-1, RV-I-029, DK-I-60-3 and DK-I-86-1; LAU 463 and related analogues DK-I-58-1 and DK-II-58-1; and DK-I-87-1), alone and in combination with diazepam, on the behaviour of maleSprague–Dawley rats. An excellent behavioural safety profile of all tested PQswas demonstrated in the spontaneous locomotor activity, rotarod, loss of right-ing reflex and pentylenetetrazol tests. In interaction studies, only PZ-II-029and its analogues prevented the ataxic effects of the benzodiazepine, asassessed in the rotarod test and during monitoring of rat locomotor activityafter awakening from the loss of righting reflex. Published electrophysiologicalprofiles of PQ ligands imply that positive modulation elicited atα6-GABAAreceptors that contain theγ2 andδsubunit, rather than their neutral modula-tory action at the benzodiazepine site, may prevent the ataxic action of diaze-pam. Thus, PZ-II-029 and its deuterated analogues are not prone to untowardinteractions with benzodiazepines and may indeed completely abolish theirataxic action, seen at therapeutic, and especially toxic concentrations.",
publisher = "John Wiley and Sons Inc",
journal = "Basic and Clinical Pharmacology and Toxicology",
title = "Behavioural interaction of pyrazoloquinolinone positive allosteric modulators at α6GABAA receptors and diazepam in rats: Anti-diazepam-induced ataxia action as a structure-dependent feature",
volume = "131",
number = "6",
pages = "514-524",
doi = "10.1111/bcpt.13801"
}

Divović-Matović, B., Knutson, D., Mitrović, J., Stevanović, V., Stanojević, B., Savić, S., Cook, J.,& Savić, M.. (2022). Behavioural interaction of pyrazoloquinolinone positive allosteric modulators at α6GABAA receptors and diazepam in rats: Anti-diazepam-induced ataxia action as a structure-dependent feature. in Basic and Clinical Pharmacology and Toxicology
John Wiley and Sons Inc., 131(6), 514-524.
https://doi.org/10.1111/bcpt.13801

Divović-Matović B, Knutson D, Mitrović J, Stevanović V, Stanojević B, Savić S, Cook J, Savić M. Behavioural interaction of pyrazoloquinolinone positive allosteric modulators at α6GABAA receptors and diazepam in rats: Anti-diazepam-induced ataxia action as a structure-dependent feature. in Basic and Clinical Pharmacology and Toxicology. 2022;131(6):514-524.
doi:10.1111/bcpt.13801 .

Divović-Matović, Branka, Knutson, Dan, Mitrović, Jelena, Stevanović, Vladimir, Stanojević, Boban, Savić, Snežana, Cook, James, Savić, Miroslav, "Behavioural interaction of pyrazoloquinolinone positive allosteric modulators at α6GABAA receptors and diazepam in rats: Anti-diazepam-induced ataxia action as a structure-dependent feature" in Basic and Clinical Pharmacology and Toxicology, 131, no. 6 (2022):514-524,
https://doi.org/10.1111/bcpt.13801 . .