Evidence map›Paper›PMID 21502953›Full record

Trial reportMolecular psychiatry2011

Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans.

E A Rabiner, J Beaver, A Makwana, G Searle, C Long, P J Nathan, R D Newbould, J Howard, S R Miller, M A Bush and 6 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Molecular psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00976066 (An Open-label, Non-randomized [11C]Carfentanil PET Study in Healthy Male Subjects to Investigate Brain Mu-opioid Receptor Occupancy, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1521498 and Naltrexone.), which is not on this map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% 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.

NCT00976066 phase1completednot on this map

An Open-label, Non-randomized [11C]Carfentanil PET Study in Healthy Male Subjects to Investigate Brain Mu-opioid Receptor Occupancy, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1521498 and Naltrexone.

TypeinterventionalSponsorGlaxoSmithKlineRan2009 to 2009Enrolled26ConditionsObesityArmsPart A Assessing GSK1521498, Part B Assessing GSK1521498, Part C Assessing Naltrexone
3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

  1. Pooled it
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  6. Intranasal naloxone rapidly occupies brain mu-opioid receptors in human subjects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019
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  19. Total-body imaging of mu-opioid receptors with [European journal of nuclear medicine and molecular imaging · 2024
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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

16 authors at 6 institutions in 2 countries.

E A RabinerGSK Clinical Imaging Centre, Imperial College London, Hammersmith Hospital, London, UK.
J Beaver
A Makwana
G Searle
C Long
P J Nathan
R D Newbould
J Howard
S R Miller
M A Bush
S Hill
R Reiley
J Passchier
R N Gunn
P M Matthews
E T Bullmore
Hammersmith Hospital · GBImperial College London · GBUniversity of Cambridge · GBAge UK · GBResearch Triangle Park Foundation · USUniversity of Oxford · GB

Funding

Medical Research Council G0900897
6 · The paper itself

Abstract

Opioid neurotransmission has a key role in mediating reward-related behaviours. Opioid receptor (OR) antagonists, such as naltrexone (NTX), can attenuate the behaviour-reinforcing effects of primary (food) and secondary rewards. GSK1521498 is a novel OR ligand, which behaves as an inverse agonist at the μ-OR sub-type. In a sample of healthy volunteers, we used [(11)C]-carfentanil positron emission tomography to measure the OR occupancy and functional magnetic resonance imaging (fMRI) to measure activation of brain reward centres by palatable food stimuli before and after single oral doses of GSK1521498 (range, 0.4-100 mg) or NTX (range, 2-50 mg). GSK1521498 had high affinity for human brain ORs (GSK1521498 effective concentration 50 = 7.10 ng ml(-1)) and there was a direct relationship between receptor occupancy (RO) and plasma concentrations of GSK1521498. However, for both NTX and its principal active metabolite in humans, 6-β-NTX, this relationship was indirect. GSK1521498, but not NTX, significantly attenuated the fMRI activation of the amygdala by a palatable food stimulus. We thus have shown how the pharmacological properties of OR antagonists can be characterised directly in humans by a novel integration of molecular and functional neuroimaging techniques. GSK1521498 was differentiated from NTX in terms of its pharmacokinetics, target affinity, plasma concentration-RO relationships and pharmacodynamic effects on food reward processing in the brain. Pharmacological differentiation of these molecules suggests that they may have different therapeutic profiles for treatment of overeating and other disorders of compulsive consumption.

Indexed as

RewardAdultAmygdalaBrainBrain MappingCorpus StriatumDose-Response Relationship, DrugFentanylFoodHumansIndansMaleMiddle AgedNaltrexoneNarcotic AntagonistsRadioligand AssaycarfentanilFentanylIndansN-((3,5-difluoro-3'-(1H-1,2,4-triazol-3-yl)-4-biphenylyl)methyl)-2,3-dihydro-1H-inden-2-amineNaltrexoneNarcotic AntagonistsTriazoles

Identifiers

PMID21502953
PMCPMC3142667
OpenAlexW1978543620

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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.