ArticleThe Journal of pharmacology and experimental therapeutics2023
Initial Pharmacological Characterization of a Major Hydroxy Metabolite of PF-5190457: Inverse Agonist Activity of PF-6870961 at the Ghrelin Receptor.
Open access · bronzeAbstract read
In one paragraph
Article in The Journal of pharmacology and experimental therapeutics, 2023. 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
0.9field-weighted citation impact, top 31% of its field
What it found
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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.
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
3 citing papers in PubMed, 6 citations in OpenAlex.
- 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
- Pharmacological GHSR (ghrelin receptor) blockade reduces alcohol binge-like drinking in male and female mice.Neuropharmacology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Sara L DeschaineClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Morten A HedegaardClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Claire L PinceClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Mehdi FarokhniaClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Jacob E MooseClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Ingrid A StockClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Sravani AdusumalliClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Fatemeh AkhlaghiClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
James L HouglandClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Agnieszka SulimaClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Kenner C RiceClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
George F KoobClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Leandro F VendruscoloClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Birgitte HolstClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.).
Lorenzo LeggioClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland (S.L.D., C.L.P., M.F., L.L.); Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (S.L.D.); Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark (M.A.H., B.H.); Neurobiology of Addiction Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse (C.L.P., G.F.K., L.F.V.) and Medication Development Program, National Institute on Drug Abuse Intramural Research Program (A.S., K.C.R., L.L.), National Institutes of Health, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health (M.F.) and Division of Addiction Medicine, Department of Medicine, School of Medicine (L.L.), Johns Hopkins University, Baltimore, Maryland; Department of Chemistry (J.E.M., J.L.H.), Department of Biology (J.L.H.), and BioInspired Syracuse (J.L.H.), Syracuse University, Syracuse, New York; Pfizer Inc. Medicine Design, Groton, Connecticut (I.A.S.); Clinical Pharmacokinetics Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (S.A., F.A.); Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (A.S., K.C.R.); and Center for Alcohol Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island (L.L.) lorenzo.leggio@nih.gov.
National Institute on Alcohol Abuse and Alcoholism · USNational Institute on Drug Abuse · USOffice of Extramural Research · USJohns Hopkins University · USSyracuse University · USUniversity of Copenhagen · DK
Funding
Medicinal Chemistry of Drugs Acting on Central and Peripheral Opioid ReceptorsZIADA000527 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI RICE, KENNER · 2009 to 2025
$23.2MClinical Psychoneuroendocrinology and Neuropsychopharmacology (CPN)ZIADA000635 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI LEGGIO, LORENZO · 2020 to 2025
$15.2MA Novel Compound for Alcoholism Treatment: a Translational StrategyUH3TR000963 · NCATS · UNIVERSITY OF RHODE ISLAND · PI AKHLAGHI, FATEMEH, LEGGIO, LORENZO · 2014 to 2016
$1.1MDefining the Molecular Architecture for Transmembrane Acylation by a Membrane Bound O-AcyltransferaseR01GM134102 · NIGMS · SYRACUSE UNIVERSITY · PI CHISHOLM, JOHN DANIEL, HOUGLAND, JAMES · 2019 to 2021
$1.0MA Novel Compound for Alcoholism Treatment: a Translational StrategyUH2TR000963 · NCATS · UNIVERSITY OF RHODE ISLAND · PI AKHLAGHI, FATEMEH, LEGGIO, LORENZO · 2013 to 2013
$550kNCATS NIH HHS UH2 TR000963NCATS NIH HHS UH3 TR000963NIGMS NIH HHS R01 GM134102
Abstract
Preclinical and clinical studies have identified the ghrelin receptor [growth hormone secretagogue receptor (GHSR)1a] as a potential target for treating alcohol use disorder. A recent phase 1a clinical trial of a GHSR1a antagonist/inverse agonist, PF-5190457, in individuals with heavy alcohol drinking identified a previously undetected major hydroxy metabolite of PF-5190457, namely PF-6870961. Here, we further characterized PF-6870961 by screening for off-target interactions in a high-throughput screen and determined its in vitro pharmacodynamic profile at GHSR1a through binding and concentration-response assays. Moreover, we determined whether the metabolite demonstrated an in vivo effect by assessing effects on food intake in male and female rats. We found that PF-6870961 had no off-target interactions and demonstrated both binding affinity and inverse agonist activity at GHSR1a. In comparison with its parent compound, PF-5190457, the metabolite PF-6870961 had lower binding affinity and potency at inhibiting GHSR1a-induced inositol phosphate accumulation. However, PF-6870961 had increased inhibitory potency at GHSR1a-induced
Indexed as
AlcoholismAnimalsAzetidinesDrug Inverse AgonismFemaleIndenesMalePyrimidinesRatsReceptors, GhrelinSpiro CompoundsThiazolesAzetidinesIndenesPF-5190457PF-6870961PyrimidinesReceptors, GhrelinSpiro CompoundsThiazoles
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