title: The macrocyclic peptide natural product CJ-15,208 is orally active and prevents reinstatement of extinguished cocaine-seeking behavior.
abstract: 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.
authors: Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045, USA. jaldrich@ku.edu
authors: Jane V
authors: JV
authors: Aldrich
authors: Sanjeewa N
authors: SN
authors: Senadheera
authors: Nicolette C
authors: NC
authors: Ross
authors: Michelle L
authors: ML
authors: Ganno
authors: Shainnel O
authors: SO
authors: Eans
authors: Jay P
authors: JP
authors: McLaughlin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C540936:CJ 15,208; D010456:Peptides, Cyclic; D003042:Cocaine