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

Jane V. Aldrich | Zendy; Sanjeewa N. Senadheera | Zendy; Nicolette C. Ross | Zendy; Michelle L. Ganno | Zendy; Shainnel O. Eans | Zendy; Jay P. McLaughlin | Zendy

Open Access

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

Author(s) -

Jane V. Aldrich,

Sanjeewa N. Senadheera,

Nicolette C. Ross,

Michelle L. Ganno,

Shainnel O. Eans,

Jay P. McLaughlin

Publication year - 2013

Publication title -

journal of natural products

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.976

H-Index - 139

eISSN - 1520-6025

pISSN - 0163-3864

DOI - 10.1021/np300697k

Subject(s) - tetrapeptide , pharmacology , natural product , antagonist , agonist , chemistry , opioid , conditioned place preference , stereochemistry , analgesic , morphine , receptor , peptide , medicine , biochemistry

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-brain 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.

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