Evidence map›Paper›PMID 25609595›Full record

ArticleThe international journal of neuropsychopharmacology2014

Quantification of central substance P receptor occupancy by aprepitant using small animal positron emission tomography.

Tadashi Endo, Takeaki Saijo, Eisuke Haneda, Jun Maeda, Masaki Tokunaga, Ming-Rong Zhang, Ayako Kannami, Hidetoshi Asai, Masayuki Suzuki, Tetsuya Suhara and 1 more

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

Article in The international journal of neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

3 citing papers in PubMed, 38 citations in OpenAlex.

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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

11 authors at 3 institutions in 1 country.

Tadashi EndoMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Takeaki SaijoMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Eisuke HanedaMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Jun MaedaMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Masaki TokunagaMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Ming-Rong ZhangMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Ayako KannamiMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Hidetoshi AsaiMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Masayuki SuzukiMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Tetsuya SuharaMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki).
Makoto HiguchiMolecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan (Drs Endo, Saijo, Haneda, Maeda, Tokunaga, Zhang, Suhara, Higuchi); Department of Molecular Neuroimaging, Tohoku University Graduate School of Medicine, Sendai, Japan (Drs Endo, Saijo, Suhara, and Higuchi); DMPK Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Kisarazu, Japan (Drs Endo, Saijo, and Kannami); Clinical & Research Quality Assurance Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Asai); Clinical Pharmacology Department, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan (Dr Suzuki). mhiguchi@nirs.go.jp.
Mitsubishi Group (Japan) · JPMitsubishi Tanabe Pharma CorporationTohoku University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCentral substance P receptors, termed NK-1 receptors, have been considered as therapeutic targets in the development of drugs against diverse conditions, including emesis, overactive bladder, and depression.

methodsHere, we applied small animal positron emission tomography (PET) and a radioligand for NK-1 receptors ([(18)F]FE-SPA-RQ) for measuring occupancies of these receptors by a selective antagonist (aprepitant) in order to examine the validity of this in vivo imaging system for preclinical characterization of candidate agents acting on NK-1 receptors, and as a tool for predicting optimal doses in humans.

resultsPET in gerbils depicted high uptake in the striatum and dose-dependent displacement with increasing doses of aprepitant. Occupancies increased as a function of aprepitant plasma concentrations according to a one-site competition model, which agrees with reported occupancy-concentration relationships in clinical studies after correction for species differences in plasma protein-unbound aprepitant fractions. These occupancy data were further supported by ex vivo autoradiography of brain samples from aprepitant-treated gerbils. In a pilot study of a marmoset, we obtained more accurate determinations of NK-1 receptor occupancy, less affected by spillover of signals from extracranial tissues than in gerbil experiments.

conclusionsThese findings support the utility of small animals and quantitative PET in the development of drugs targeting NK-1 receptors.

Indexed as

AnimalsAprepitantAutoradiographyBrainCallithrixDose-Response Relationship, DrugGerbillinaeHumansMaleMorpholinesNeurokinin-1 Receptor AntagonistsPilot ProjectsPositron-Emission TomographyReceptors, Neurokinin-1AprepitantMorpholinesNeurokinin-1 Receptor AntagonistsReceptors, Neurokinin-1NK-1 receptorreceptor occupancysmall-animal PETsubstance P

Identifiers

PMID25609595
PMCPMC4368889
OpenAlexW2242653769

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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.