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Opioid Receptor Modulation of Hedonic Taste Preference and Food Intake: A Single‐Dose Safety, Pharmacokinetic, and Pharmacodynamic Investigation With GSK1521498, a Novel μ‐Opioid Receptor Inverse Agonist
Author(s) -
Nathan Pradeep J.,
O'Neill Barry V.,
Bush Mark A.,
Koch Annelize,
Tao Wenli X.,
Maltby Kay,
Napolitano Antonella,
Brooke Allison C.,
Skeggs Andrew L.,
Herman Craig S.,
Larkin Andrew L.,
Ignar Diane M.,
Richards Duncan B.,
Williams Pauline M.,
Bullmore Edward T.
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011399577
Subject(s) - overeating , pharmacokinetics , pharmacodynamics , pharmacology , inverse agonist , opioid , agonist , endogenous opioid , medicine , endocrinology , receptor , chemistry , obesity
Endogenous opioids and μ‐opioid receptors have been linked to hedonic and rewarding aspects of palatable food intake. The authors examined the safety, pharmacokinetic, and pharmacodynamic profile of GSK1521498, a μ‐opioid receptor inverse agonist that is being investigated primarily for the treatment of overeating behavior in obesity. In healthy participants, GSK1521498 oral solution and capsule formulations were well tolerated up to a dose of 100 mg. After single doses (10–150 mg), the maximum concentration (C max ) and area under the curve (AUC) in plasma increased in a dose‐proportional manner. GSK1521498 selectively reduced sensory hedonic ratings of high‐sugar and high‐fat dairy products and caloric intake of high‐fat/high‐sucrose snack foods. These findings provide encouraging data in support of the development of GSK1521498 for the treatment of disorders of maladaptive ingestive behavior or compulsive consumption.