Evidence map›Paper›PMID 35194800›Full record

ArticleBiopharmaceutics & drug disposition2022

Metabolism, pharmacokinetics, and anticonvulsant activity of a deuterated analog of the α2/3-selective GABAkine KRM-II-81.

Lalit K Golani, Branka Divović, Dishary Sharmin, Kamal P Pandey, Md Yeunus Mian, Rok Cerne, Nicolas M Zahn, Michelle J Meyer, Veera V N P B Tiruveedhula, Jodi L Smith and 8 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biopharmaceutics & drug disposition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 38% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Key Characteristics and Development of Psychoceuticals: A Review.International journal of molecular sciences · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 3 countries.

Lalit K GolaniDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.ORCID https://orcid.org/0000-0002-6233-7747
Branka DivovićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Dishary SharminDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Kamal P PandeyDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Md Yeunus MianDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Rok CerneLaboratory of Antiepileptic Drug Discovery, Ascencion St. Vincent, Indianapolis, Indiana, USA.
Nicolas M ZahnDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Michelle J MeyerDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Veera V N P B TiruveedhulaDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Jodi L SmithLaboratory of Antiepileptic Drug Discovery, Ascencion St. Vincent, Indianapolis, Indiana, USA.
Xingjie PingDepartment of Anatomy and Cell Biology, Indiana University/Purdue University, Indianapolis, Indiana, USA.
Xiaoming JinDepartment of Anatomy and Cell Biology, Indiana University/Purdue University, Indianapolis, Indiana, USA.
Arnold LippaRespireRx Pharmaceuticals Inc, Glen Rock, New Jersey, USA.
Jeffrey M SchkeryantzBristol Myers Squibb, Cambridge, Massachusetts, USA.
Leggy A ArnoldDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.ORCID https://orcid.org/0000-0003-1411-1572
James M CookDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Miroslav M SavićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Jeffrey M WitkinDepartment of Chemistry & Biochemistry, Milwaukee Institute of Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.ORCID https://orcid.org/0000-0002-9048-148X
University of Wisconsin–Milwaukee · USEloxx Pharmaceuticals (United States) · USUniversity of Indianapolis · USUniversity of Belgrade · RSBristol-Myers Squibb (United States) · USSt. Vincent Hospital · US

Funding

Tolerance and Physical Dependence after Chronic Benzodiazepine TreatmentR01DA043204 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI JAMES K ROWLETT · 2017 to 2026
$4.3M
Synthesis of Alpha2/Alpha3 GABA Agonists to Treat Neuropathic PainR01NS076517 · NINDS · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2012 to 2015
$1.3M
NIDA NIH HHS R01 DA043204NIH HHS DA-043204NIH HHS NS-076517NINDS NIH HHS R01 NS076517NSF CHE-1625735
6 · The paper itself

Abstract

The imidazodiazepine, (5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo [f]imidazole[1,5-α][1,4]diazepin-3-yl) oxazole or KRM-II-81) is a new α2/3-selective GABAkine (gamma aminobutyric acid A receptor potentiator) with anticonvulsant, anxiolytic, and antinociceptive activity in preclinical models. Reducing metabolism was utilized as a means of potentially extending the half-life of KRM-II-81. In vitro and in vivo studies were conducted to evaluate metabolic liabilities. Incubation of KRM-II-81 in hepatocytes revealed sites of potential metabolism on the oxazole and the diazepine rings. These sites were targeted in the design of a deuterated analog (D5-KRM-II-81) that could be evaluated as a potentially longer-acting analog. In contrast to computer predictions, peak plasma concentrations of D5-KRM-II-81 in rats were not significantly greater than those produced by KRM-II-81 after oral administration. Furthermore, brain disposition of KRM-II-81 was higher than that of D5-KRM-II-81. The half-life of the two compounds in either plasma or brain did not statistically differ from one another but the t

Indexed as

Antibiotics, AntitubercularAnticonvulsantsAnimalsOxazolesRatsReceptors, GABA-AAntibiotics, AntitubercularAnticonvulsantsKRM-II-81OxazolesReceptors, GABA-AepilepsyGABAKRM-II-81metabolismpharmacokinetics

Identifiers

PMID35194800
PMCPMC12990634
OpenAlexW4213432284

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.