The Macrocyclic Peptide Natural Product CJ-15,208 Is Orally Active and Prevents Reinstatement of Extinguished Cocaine-Seeking Behavior

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• 作者：Jane V. Aldrich ; Sanjeewa N. Senadheera ; Nicolette C. Ross ; Michelle L. Ganno ; Shainnel O. Eans ; Jay P. McLaughlin
• 刊名：Journal of Natural Products
• 出版年：2013
• 出版时间：March 22, 2013
• 年：2013
• 卷：76
• 期：3
• 页码：433-438
• 全文大小：326K
• 年卷期：v.76,no.3(March 22, 2013)
• ISSN：1520-6025

文摘

The macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-d-Pro-Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration. CJ-15,208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood鈥揵rain barrier to reach KOR in the CNS. Orally administered CJ-15,208 also prevented both cocaine- and stress-induced reinstatement of extinguished cocaine-seeking behavior in the conditioned place preference assay in a time- and dose-dependent manner. Thus, CJ-15,208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug-seeking behavior in abstinent subjects.