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
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 treatmen...
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| Veröffentlicht in: | Journal of clinical pharmacology 2012-04, Vol.52 (4), p.464-474 |
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| creator | 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. |
| description | 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 (Cmax) 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. |
| doi_str_mv | 10.1177/0091270011399577 |
| format | Article |
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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 (Cmax) 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.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1177/0091270011399577</identifier><identifier>PMID: 21610207</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Administration, Oral ; Adult ; Area Under Curve ; binge eating ; Cross-Over Studies ; Dairy products ; Data processing ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Inverse Agonism ; Eating - drug effects ; Food intake ; Food Preferences - drug effects ; hedonic ; Hedonic response ; Humans ; Indans - adverse effects ; Indans - pharmacokinetics ; Indans - pharmacology ; Inverse agonists ; Male ; Obesity ; Opioid receptors ; Opioid receptors (type mu) ; pharmacodynamic ; Pharmacodynamics ; Pharmacokinetics ; Receptors, Opioid, mu - agonists ; reward ; Single-Blind Method ; taste preference ; Taste preferences ; Triazoles - adverse effects ; Triazoles - pharmacokinetics ; Triazoles - pharmacology ; μ-Opioid receptor</subject><ispartof>Journal of clinical pharmacology, 2012-04, Vol.52 (4), p.464-474</ispartof><rights>2012 The Author(s)</rights><rights>2012 American College of Clinical Pharmacology</rights><rights>2012 SAGE Publications</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5272-60700a8fd3734ec6b237689fd3305713b184f19d818ba1e3421d2201a7a4da033</citedby><cites>FETCH-LOGICAL-c5272-60700a8fd3734ec6b237689fd3305713b184f19d818ba1e3421d2201a7a4da033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1177%2F0091270011399577$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1177%2F0091270011399577$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21610207$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nathan, Pradeep J.</creatorcontrib><creatorcontrib>O'Neill, Barry V.</creatorcontrib><creatorcontrib>Bush, Mark A.</creatorcontrib><creatorcontrib>Koch, Annelize</creatorcontrib><creatorcontrib>Tao, Wenli X.</creatorcontrib><creatorcontrib>Maltby, Kay</creatorcontrib><creatorcontrib>Napolitano, Antonella</creatorcontrib><creatorcontrib>Brooke, Allison C.</creatorcontrib><creatorcontrib>Skeggs, Andrew L.</creatorcontrib><creatorcontrib>Herman, Craig S.</creatorcontrib><creatorcontrib>Larkin, Andrew L.</creatorcontrib><creatorcontrib>Ignar, Diane M.</creatorcontrib><creatorcontrib>Richards, Duncan B.</creatorcontrib><creatorcontrib>Williams, Pauline M.</creatorcontrib><creatorcontrib>Bullmore, Edward T.</creatorcontrib><title>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</title><title>Journal of clinical pharmacology</title><addtitle>J Clin Pharmacol</addtitle><description>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 (Cmax) 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.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Area Under Curve</subject><subject>binge eating</subject><subject>Cross-Over Studies</subject><subject>Dairy products</subject><subject>Data processing</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Drug Inverse Agonism</subject><subject>Eating - drug effects</subject><subject>Food intake</subject><subject>Food Preferences - drug effects</subject><subject>hedonic</subject><subject>Hedonic response</subject><subject>Humans</subject><subject>Indans - adverse effects</subject><subject>Indans - pharmacokinetics</subject><subject>Indans - pharmacology</subject><subject>Inverse agonists</subject><subject>Male</subject><subject>Obesity</subject><subject>Opioid receptors</subject><subject>Opioid receptors (type mu)</subject><subject>pharmacodynamic</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Receptors, Opioid, mu - agonists</subject><subject>reward</subject><subject>Single-Blind Method</subject><subject>taste preference</subject><subject>Taste preferences</subject><subject>Triazoles - adverse effects</subject><subject>Triazoles - pharmacokinetics</subject><subject>Triazoles - pharmacology</subject><subject>μ-Opioid receptor</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v0zAYxyMEYmNw54QscYDDAn6NE25Vx9rCXgod6tFykyet1zQudrLR78ZHQHwmHNpNqBJwsmz__v_nNYqeE_yGECnfYpwRKjEmhGWZkPJBdEiEoDFPMH8YHXbfcfd_ED3x_jpwCRfkcXRASUIwxfIw-nG5NtYU6DPksG6sQ-e2aCvdGFsjW6IhFLY2ObrSvgE0dlCCgzoHpOsCnVpboFHd6CW8Qz00MfW8gvjEekATXUKzOUbjhXYrndulqaEx-fFv3d1jsan1KpiP6hvwjZlvo05Ns0CDyUciKOFZGiTowt5AhX5-j_eT7ZQuhOvNQ5a-eRo9KnXl4dnuPIq-nL6_6g_js8vBqN87i3NBJY0THFqi07JgknHIkxllMkmzcGdYSMJmJOUlyYqUpDNNgHFKCkox0VLzQmPGjqJXW9-1s1_bkLtaGZ9DVekabOtVJjLCmWBJIF__kySYyDC4VHamL_fQa9u6OtShiMSJJJSJLFB4S-XOeh_modbOrLTbBCvV7YTa34kgebEzbmcrKO4Fd0sQAL4Fbm3VhH4uq_YWnFqArppF8MOYB784dIBiHm5x90SDLNnJTAWb_-ahPvTHQ8HTrinxVuj1HP6o8u8F7PgwYvh2H0i7pUokk0JNLwbq03Ry3p-Mp-qE_QIayeuo</recordid><startdate>201204</startdate><enddate>201204</enddate><creator>Nathan, Pradeep J.</creator><creator>O'Neill, Barry V.</creator><creator>Bush, Mark A.</creator><creator>Koch, Annelize</creator><creator>Tao, Wenli X.</creator><creator>Maltby, Kay</creator><creator>Napolitano, Antonella</creator><creator>Brooke, Allison C.</creator><creator>Skeggs, Andrew L.</creator><creator>Herman, Craig S.</creator><creator>Larkin, Andrew L.</creator><creator>Ignar, Diane M.</creator><creator>Richards, Duncan B.</creator><creator>Williams, Pauline M.</creator><creator>Bullmore, Edward T.</creator><general>Blackwell Publishing Ltd</general><general>SAGE Publications</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7T2</scope><scope>7U2</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>201204</creationdate><title>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</title><author>Nathan, Pradeep J. ; 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| ispartof | Journal of clinical pharmacology, 2012-04, Vol.52 (4), p.464-474 |
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| subjects | Administration, Oral Adult Area Under Curve binge eating Cross-Over Studies Dairy products Data processing Dose-Response Relationship, Drug Double-Blind Method Drug Inverse Agonism Eating - drug effects Food intake Food Preferences - drug effects hedonic Hedonic response Humans Indans - adverse effects Indans - pharmacokinetics Indans - pharmacology Inverse agonists Male Obesity Opioid receptors Opioid receptors (type mu) pharmacodynamic Pharmacodynamics Pharmacokinetics Receptors, Opioid, mu - agonists reward Single-Blind Method taste preference Taste preferences Triazoles - adverse effects Triazoles - pharmacokinetics Triazoles - pharmacology μ-Opioid receptor |
| title | 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 |
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