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.

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.

Lee, Mary R;Farokhnia, Mehdi;Cobbina, Enoch;Saravanakumar, Anitha;Li, Xiaobai;Battista, Jillian T;Farinelli, Lisa A;Akhlaghi, Fatemeh;Leggio, Lorenzo;
Neuropharmacology 2019 pp. 107788
270
lee2019endocrineneuropharmacology

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 relevance of these findings to the use of PF-5190457 as a probe for endogenous ghrelin signaling in alcohol use disorder is discussed. CLINICALTRIALS.GOV: NCT02039349.

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