Evidence map›Paper›PMID 26233800›Full record

ArticleBioorganic & medicinal chemistry2015

Synthesis, nicotinic acetylcholine receptor binding, in vitro and in vivo pharmacology properties of 3'-(substituted pyridinyl)-deschloroepibatidine analogs.

Pauline W Ondachi, Zhuo Ye, Ana H Castro, Charles W Luetje, M Imad Damaj, S Wayne Mascarella, Hernán A Navarro, F Ivy Carroll

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

Article in Bioorganic & medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 45% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
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

8 authors at 3 institutions in 1 country.

Pauline W OndachiCenter for Drug Discovery, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
Zhuo YeDepartment of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33101, United States.
Ana H CastroDepartment of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33101, United States.
Charles W LuetjeDepartment of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33101, United States.
M Imad DamajDepartment of Pharmacology and Toxicology, Virginia Commonwealth University Medical Campus, PO Box 980615, Richmond, VA 23298, United States.
S Wayne MascarellaCenter for Drug Discovery, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
Hernán A NavarroCenter for Drug Discovery, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
F Ivy CarrollCenter for Drug Discovery, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States. Electronic address: fic@rti.org.
RTI International · USUniversity of Miami · USVirginia Commonwealth University Medical Center · US

Funding

DEVELOPMENT OF LIGANDS FOR NICOTINIC RECEPTORSR01DA012001 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI CARROLL, FRANK IVY · 1999 to 2012
$4.8M
NIDA NIH HHS DA12001NIDA NIH HHS R01 DA012001
6 · The paper itself

Abstract

Over the last several years we have synthesized and studied the in vitro and in vivo nAChR pharmacological properties of epibatidine (4) analogs. In this study we report the synthesis, nAChR in vitro and in vivo pharmacological properties of 3'-(substituted pyridinyl)-deschloroepibatidine analogs (5a-e and 6a-e). All of the analogs had high binding affinity for α4β2(∗)-nAChRs. Several of the analogs were potent antagonists of α4β2-nAChRs in in vitro efficacy tests and were potent antagonists of nicotine-induced antinociception in the mouse tail-flick test. Compound 6b had a Ki = 0.13 nM in the binding assay, 25- and 46-fold selectivity for the α4β2(∗)-nAChR relative to the α3β4- and α7-nAChR, respectively, in the in vitro efficacy test and an AD50 = 0.13 μg/kg in the tail-flick test. Combined with favorable calculated physiochemical properties compared to varenicline, our findings suggest that 6b should be considered for development as a potential pharmacotherapy for treating nicotine addiction and other CNS disorders.

Indexed as

AnimalsBridged Bicyclo Compounds, HeterocyclicHumansMiceMolecular StructureNicotianaPyridinesRatsReceptors, NicotinicStructure-Activity RelationshipBridged Bicyclo Compounds, HeterocyclicdeschloroepibatidinePyridinesReceptors, NicotinicEpibatidine analogsIn vitro/in vivo studynAChR antagonistNicotine receptorVarenicline

Identifiers

PMID26233800
PMCPMC4554999
OpenAlexW1128836429

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.