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Neuropharmacology
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Neuropharmacology
Article . 2020 . Peer-reviewed
License: Elsevier TDM
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Endocrine effects of the novel ghrelin receptor inverse agonist PF-5190457: Results from a placebo-controlled human laboratory alcohol co-administration study in heavy drinkers

Authors: Mary R. Lee; Mehdi Farokhnia; Enoch Cobbina; Anitha Saravanakumar; Xiaobai Li; Jillian T. Battista; Lisa A. Farinelli; +2 Authors

Endocrine effects of the novel ghrelin receptor inverse agonist PF-5190457: Results from a placebo-controlled human laboratory alcohol co-administration study in heavy drinkers

Abstract

Both animal and human work suggests that the ghrelin system may be involved in the mechanisms that regulate the development and maintenance of alcohol use disorder. Previously, in a Phase 1b study, we tested pharmacological blockade of the growth hormone secretagogue receptor 1a (GHS-R1a, also known as the ghrelin receptor), in heavy drinking individuals with PF-5190457, an orally bioavailable, potent and selective GHS-R1a inverse agonist. We report here the effects of PF-5190457 on endocrine blood concentrations of amylin, gastric inhibitory polypeptide, glucagon-like peptide 1, insulin, leptin, pancreatic polypeptide, peptide YY, thyroid stimulating hormone, free triiodothyronine (T3), thyroxine (T4), cortisol, prolactin, and glucose during PF-5190457 dosing, as compared to placebo, in absence of alcohol as well as during an alcohol challenge when PF-5190457 was on steady-state. Blood hormone levels were largely unaffected by PF-5190457, both during dosing and in the context of alcohol challenge. The safety-related relevance of these findings to further develop PF-5190547 in alcohol use disorder is discussed. CLINICALTRIALS.GOV: NCT02039349. This article is part of the special issue on 'Neuropeptides'.

Country
United States
Keywords

Adult, Leptin, Male, Drug Inverse Agonism, 610, GHS-R1a, PF-5190457, 576, Alcohol use disorder, Humans, Single-Blind Method, Spiro Compounds, Receptors, Ghrelin, Dose-Response Relationship, Drug, Ethanol, Heavy drinking, Neuroendocrinology, Ghrelin, Hormones, Islet Amyloid Polypeptide, Prolactin, Azetidines, Female, Alcohol, Alcoholic Intoxication

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    25
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
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    impulse
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    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
25
Top 10%
Average
Top 10%
bronze