ArticleMolecular psychiatry2020
The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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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.
Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Animal studies reveal that the ghrelin pathway regulates alcohol-mediated responses.Frontiers in psychiatry · 2023Pooled it
- An Overview of Appetite-Regulatory Peptides in Addiction Processes; From Bench to Bed Side.Frontiers in neuroscience · 2021Pooled it
- Pharmacokinetic and pharmacodynamic results from a randomized controlled study with the growth hormone secretagogue receptor blocker PF-5190457 in recently abstinent patients with alcohol use disorder.The international journal of neuropsychopharmacology · 2026Trial
- A randomized, double-blind, placebo-controlled study of a GHSR blocker in people with alcohol use disorder.JCI insight · 2024Trial
- Ghrelin decreases sensitivity to negative feedback and increases prediction-error related caudate activity in humans, a randomized controlled trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- A closer look at alcohol-induced changes in the ghrelin system: novel insights from preclinical and clinical data.Addiction biology · 2022Trial
- Effect of intravenous ghrelin administration, combined with alcohol, on circulating metabolome in heavy drinking individuals with alcohol use disorder.Alcoholism, clinical and experimental research · 2021Trial
- A population-based investigation of the association between alcohol intake and serum total ghrelin concentrations among cigarette-smoking, non-alcohol-dependent male individuals.Drug and alcohol dependence · 2021Trial
- Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study.The international journal of neuropsychopharmacology · 2021Trial
- Trial
- Pharmacological manipulation of the ghrelin system and alcohol hangover symptoms in heavy drinking individuals: Is there a link?Pharmacology, biochemistry, and behavior · 2018Trial
- Alcohol Exposure Alters the Ghrelin System: In Vitro Mechanistic Insights Into Impaired Glucose Sensing and Enhanced Ghrelin Secretion.Alcohol, clinical & experimental research · 2026Article
- GHSR antagonist LEAP2 concentrations negatively correlate with alcohol craving and are modulated by alcohol exposure: Evidence from human and rat studies.Drug and alcohol dependence · 2026Article
- A Dimer for Dinner: The Impact of GHS-R1a Heterodimerization on Feeding Circuits.Biomolecules · 2026Review
- Ghrelin Receptor Deletion or Pharmacological Inhibition Improves Muscle Function in Aging Male Mice.Aging cell · 2026Article
- CBMolecular psychiatry · 2026Article
- Beyond Hunger: The Structure, Signaling, and Systemic Roles of Ghrelin.International journal of molecular sciences · 2025Review
- Neuroendocrinology meets addiction: Emerging pharmacotherapies on the horizon.Journal of internal medicine · 2025Review
- The alcohol cue-exposure paradigm as a screening tool for alcohol use disorder medication development: A critical review.Alcohol, clinical & experimental research · 2025Review
- Ghrelin in Depression: A Promising Therapeutic Target.Molecular neurobiology · 2025Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Rodent studies indicate that ghrelin receptor blockade reduces alcohol consumption. However, no ghrelin receptor blockers have been administered to heavy alcohol drinking individuals. Therefore, we evaluated the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and behavioral effects of a novel ghrelin receptor inverse agonist, PF-5190457, when co-administered with alcohol. We tested the effects of PF-5190457 combined with alcohol on locomotor activity, loss-of-righting reflex (a measure of alcohol sedative actions), and on blood PF-5190457 concentrations in rats. Then, we performed a single-blind, placebo-controlled, within-subject human study with PF-5190457 (placebo/0 mg b.i.d., 50 mg b.i.d., 100 mg b.i.d.). Twelve heavy drinkers during three identical visits completed an alcohol administration session, subjective assessments, and an alcohol cue-reactivity procedure, and gave blood samples for PK/PD testing. In rats, PF-5190457 did not interact with the effects of alcohol on locomotor activity or loss-of-righting reflex. Alcohol did not affect blood PF-5190457 concentrations. In humans, all adverse events were mild or moderate and did not require discontinuation or dose reductions. Drug dose did not alter alcohol concentration or elimination, alcohol-induced stimulation or sedation, or mood during alcohol administration. Potential PD markers of PF-5190457 were acyl-to-total ghrelin ratio and insulin-like growth factor-1. PF-5190457 (100 mg b.i.d.) reduced alcohol craving during the cue-reactivity procedure. This study provides the first translational evidence of safety and tolerability of the ghrelin receptor inverse agonist PF-5190457 when co-administered with alcohol. PK/PD/behavioral findings support continued research of PF-5190457 as a potential pharmacological agent to treat alcohol use disorder.
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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.