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The impact of radiochemistry in drug projects: The use of C-14 label in the AZD8529, AZD7325, and AZD6280 projects.
Kingston L, Gu C, Guo J, Swallow S, Elmore CS. Kingston L, et al. J Labelled Comp Radiopharm. 2021 Feb;64(2):65-72. doi: 10.1002/jlcr.3902. Epub 2021 Jan 7. J Labelled Comp Radiopharm. 2021. PMID: 33326121 Review.
In this manuscript, we highlight the role radiolabeling played in determining the metabolism and in quantifying the metabolites of AZD8529, AZD7325, and AZD6280. A quantitative whole-body autoradiography study can detect covalent adducts in vivo as was the case with AZD524 …
In this manuscript, we highlight the role radiolabeling played in determining the metabolism and in quantifying the metabolites of AZD8529, …
Population pharmacokinetic modelling to assess clinical drug-drug interaction between AZD7325 and midazolam.
Zhou D, Lu Z, Sunzel M, Xu H, Al-Huniti N. Zhou D, et al. J Clin Pharm Ther. 2014 Aug;39(4):404-10. doi: 10.1111/jcpt.12152. Epub 2014 Apr 1. J Clin Pharm Ther. 2014. PMID: 24689515
The aims of this analysis were to develop population pharmacokinetic (PPK) models of AZD7325 and midazolam and to assess the induction effect of AZD7325 on CYP3A4 with midazolam as a substrate. ...The model could provide basis for the rational dosing of AZD7325 …
The aims of this analysis were to develop population pharmacokinetic (PPK) models of AZD7325 and midazolam and to assess the inductio …
Synthesis of C-14 labeled GABA(A) alpha2/alpha3 selective partial agonists and the investigation of late-occurring and long-circulating metabolites of GABA(A) receptor modulator AZD7325.
Artelsmair M, Gu C, Lewis RJ, Elmore CS. Artelsmair M, et al. J Labelled Comp Radiopharm. 2018 May 15;61(5):415-426. doi: 10.1002/jlcr.3602. Epub 2018 Mar 30. J Labelled Comp Radiopharm. 2018. PMID: 29314165 Free PMC article.
Several target compounds were identified and required in C-14 labeled form to enable a better understanding of their drug metabolism and pharmacokinetic properties. AZD7325 is a selective GABA(A) alpha2 and alpha3 receptor modulator intended for the treatment of anxiety th …
Several target compounds were identified and required in C-14 labeled form to enable a better understanding of their drug metabolism and pha …
A clinical study to assess CYP1A2 and CYP3A4 induction by AZD7325, a selective GABA(A) receptor modulator - an in vitro and in vivo comparison.
Zhou D, Sunzel M, Ribadeneira MD, Smith MA, Desai D, Lin J, Grimm SW. Zhou D, et al. Br J Clin Pharmacol. 2012 Jul;74(1):98-108. doi: 10.1111/j.1365-2125.2011.04155.x. Br J Clin Pharmacol. 2012. PMID: 22122233 Free PMC article.
There was no apparent change in AZD7325 exposure following co-administration of midazolam or caffeine compared with AZD7325 alone. ...The results triggered the further clinical evaluation of AZD7325 induction potential. AZD7325 reached a plasma C(max) …
There was no apparent change in AZD7325 exposure following co-administration of midazolam or caffeine compared with AZD7325 al …
The central nervous system effects of the partial GABA-Aalpha2,3 -selective receptor modulator AZD7325 in comparison with lorazepam in healthy males.
Chen X, Jacobs G, de Kam M, Jaeger J, Lappalainen J, Maruff P, Smith MA, Cross AJ, Cohen A, van Gerven J. Chen X, et al. Br J Clin Pharmacol. 2014 Dec;78(6):1298-314. doi: 10.1111/bcp.12413. Br J Clin Pharmacol. 2014. PMID: 24802722 Free PMC article. Clinical Trial.
AIMS: AZD7325 is a novel alpha2,3 -subtype-selective partial GABA-A-receptor modulator. ...AZD7325 10 mg and lorazepam induced different response patterns on VAS 'feeling high' and electro-encephalography. ...
AIMS: AZD7325 is a novel alpha2,3 -subtype-selective partial GABA-A-receptor modulator. ...AZD7325 10 mg and lorazepam induced …
Derisking Psychiatric Drug Development: The NIMH's Fast Fail Program, A Novel Precompetitive Model.
Grabb MC, Cross AJ, Potter WZ, McCracken JT. Grabb MC, et al. J Clin Psychopharmacol. 2016 Oct;36(5):419-21. doi: 10.1097/JCP.0000000000000536. J Clin Psychopharmacol. 2016. PMID: 27404513 Free PMC article.
This commentary presents an example of such an approach through which the National Institute of Mental Health contracted a network of academic researchers to work with other stakeholders to investigate AZD7325, a drug targeting the GABA-A alpha2/alpha3 receptor subtype, in …
This commentary presents an example of such an approach through which the National Institute of Mental Health contracted a network of academ …
GABAA receptor occupancy by subtype selective GABAAα2,3 modulators: PET studies in humans.
Jucaite A, Cselényi Z, Lappalainen J, McCarthy DJ, Lee CM, Nyberg S, Varnäs K, Stenkrona P, Halldin C, Cross A, Farde L. Jucaite A, et al. Psychopharmacology (Berl). 2017 Feb;234(4):707-716. doi: 10.1007/s00213-016-4506-4. Epub 2016 Dec 24. Psychopharmacology (Berl). 2017. PMID: 28013354 Free PMC article. Clinical Trial.
OBJECTIVES: The current study aimed to confirm target engagement at GABA(A) receptors by AZD7325 and AZD6280 in humans and to determine the relationship between exposure, GABA(A) receptor occupancy, and tolerability. ...Maximum receptor occupancy could be reached for both …
OBJECTIVES: The current study aimed to confirm target engagement at GABA(A) receptors by AZD7325 and AZD6280 in humans and to determi …
The effects of the nonselective benzodiazepine lorazepam and the alpha2 /alpha3 subunit-selective GABAA receptor modulators AZD7325 and AZD6280 on plasma prolactin levels.
Te Beek ET, Chen X, Jacobs GE, Nahon KJ, de Kam ML, Lappalainen J, Cross AJ, van Gerven JM, Hay JL. Te Beek ET, et al. Clin Pharmacol Drug Dev. 2015 Mar;4(2):149-54. doi: 10.1002/cpdd.134. Epub 2014 Aug 28. Clin Pharmacol Drug Dev. 2015. PMID: 27128218 Clinical Trial.
To explore the exact role of the GABAA receptor subtypes in the regulation of prolactin secretion and the differential effects of selective and nonselective GABA receptor modulators, the effects of the nonselective benzodiazepine lorazepam, as well as two novel alpha2 /alpha3 sub …
To explore the exact role of the GABAA receptor subtypes in the regulation of prolactin secretion and the differential effects of selective …
Late-occurring and Long-circulating Metabolites of GABA(A)(alpha)(2,3) Receptor Modulator AZD7325 Involving Metabolic Cyclization and Aromatization: Relevance to MIST Analysis and Application for Patient Compliance.
Gu C, Artelsmair M, Elmore CS, Lewis RJ, Davis P, Hall JE, Dembofsky BT, Christoph G, Smith MA, Chapdelaine M, Sunzel M. Gu C, et al. Drug Metab Dispos. 2018 Mar;46(3):303-315. doi: 10.1124/dmd.117.078873. Epub 2018 Jan 8. Drug Metab Dispos. 2018. PMID: 29311137 Clinical Trial.
AZD7325 [4-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylcinnoline-3-carboxamide] is a selective GABA(A)(alpha)(2,3) receptor modulator intended for the treatment of anxiety disorders through oral administration. ...The observation of late-occurring and long-circulating metab …
AZD7325 [4-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylcinnoline-3-carboxamide] is a selective GABA(A)(alpha)(2,3) receptor modulator …
Potentiating α2 subunit containing perisomatic GABAA receptors protects against seizures in a mouse model of Dravet syndrome.
Nomura T, Hawkins NA, Kearney JA, George AL Jr, Contractor A. Nomura T, et al. J Physiol. 2019 Aug;597(16):4293-4307. doi: 10.1113/JP277651. Epub 2019 May 20. J Physiol. 2019. PMID: 31045243 Free PMC article.
AZD7325 demonstrates stronger effects on IPSCs in the seizure resistant mouse strain, consistent with higher alpha(2) subunit expression. AZD7325 demonstrates seizure protective effects in Scn1a(+/-) mice without apparent sedative effects in vivo. ...
AZD7325 demonstrates stronger effects on IPSCs in the seizure resistant mouse strain, consistent with higher alpha(2) subunit express …
13 results