@article{1a28f45b792c4d26a2f4d005634ecc4b,
title = "A cholecystokinin B receptor antagonist and cocaine interaction, phase I study",
abstract = " Aims: RPR 102681, a cholecystokinin-B antagonist, increased dopamine (DA) release and reduced cocaine self-administration in animals. This pilot study sought to assess the safety and pharmacokinetics (PK) of co-administration of RPR 102681 and cocaine, and to confirm the DA release mechanism of RPR 102681. Methods: Sixteen cocaine-dependent participants were randomized to either placebo or RPR102681 at 3 ascending doses; cocaine was co-administered at steady state of RPR 102681. [ 11 C]raclopride positron emission tomography scans were conducted at baseline and at each RPR102681 dose. Results: RPR 102681 was well tolerated, and safe to co-administer with cocaine. RPR 102681 did not alter the PK of either cocaine or its metabolite benzoylecgonine and showed no intrinsic abuse liability. There was a trend toward reduction of cocaine craving scores. In contrast to animal studies, RPR 102681 significantly increased the binding potential of [ 11 C]raclopride in the ventral striatum (t test, P <.001) and caudate nucleus (t test, P <.0001) in a small subset of patients, suggesting that it may reduce intrasynaptic striatal DA. Conclusion: Overall, this pilot study suggests that RPR 102681 would be unlikely candidate, as an agonist medication for the treatment for cocaine addiction but worth investigating further for possible role in reducing craving.",
keywords = "RPR 102681, addiction, craving, dopamine, positron emission tomography",
author = "Ahmed Elkashef and Bra{\v s}i{\'c}, {James Robert} and Cantelina, {Louis R.} and Roberta Kahn and Nora Chiang and Weiguo Ye and Yun Zhou and Jurij Mojsiak and Warren, {Kimberly R.} and Andrew Crabb and John Hilton and Wong, {Dean F.} and Frank Vocci",
note = "Funding Information: (Drs. Elkashef and Kahn) to the USUHS (Dr. Cantilena), and by Grant G183?B from USUHS to The Johns Hopkins University School of Medicine and by the National Institutes of Health (K24DA00412) (Dr. Wong). Funding Information: Funding information This study was sponsored by The Medications Development Division of The National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, under the phase I studies contract to the Uniformed Services University of Health Sciences (USUHS) Clinical Pharmacology Unit, Bethesda, Maryland, and the Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland. This study was sponsored and funded through a contract from the Division of Pharmacotherapies and Medical Consequences of Drug Abuse of the National Institute on Drug Abuse (NIDA) (Drs. Elkashef and Kahn) to the USUHS (Dr. Cantilena), and by Grant G183QB from USUHS to The Johns Hopkins University School of Medicine and by the National Institutes of Health (K24DA00412) (Dr. Wong). Funding Information: This study was sponsored by The Medications Development Division of The National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, under the phase I studies contract to the Uniformed Services University of Health Sciences (USUHS) Clinical Pharmacology Unit, Bethesda, Maryland, and the Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland. This study was sponsored and funded through a contract from the Division of Pharmacotherapies and Medical Consequences of Drug Abuse of the National Institute on Drug Abuse (NIDA) Publisher Copyright: {\textcopyright} 2018. This article is a U.S. Government work and is in the public domain in the USA.",
year = "2019",
month = jan,
doi = "10.1111/cns.12994",
language = "English (US)",
volume = "25",
pages = "136--146",
journal = "CNS Neuroscience and Therapeutics",
issn = "1755-5930",
publisher = "Wiley-Blackwell",
number = "1",
}