Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2013322 | Pharmacology Biochemistry and Behavior | 2008 | 7 Pages |
Abstract
Three analogues of the dual μ-/δ-antagonist, H-Dmt-Tic-R-NH-CH2-Ph (R = 1, Lys-Z; 2, Lys-Ac; 3, Lys) were examined in vivo: 1 and 2 exhibited weak bioactivity, while 3 injected intracerebroventricularly was a potent dual antagonist for morphine- and deltorphin C-induced antinociception comparable to naltrindole (δ-antagonist), but 93% as effective as naloxone (nonspecific opioid receptor antagonist) and 4% as active as CTOP, a μ antagonist. Subcutaneous or oral administration of 3 antagonized morphine-induced antinociception indicating passage across epithelial and blood-brain barriers. Mice pretreated with 3 before morphine did not develop morphine tolerance indicative of a potential clinical role to inhibit development of drug tolerance.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Yunden Jinsmaa, Ewa D. Marczak, Gianfranco Balboni, Severo Salvadori, Lawrence H. Lazarus,