Blood-brain barrier penetration by two dermorphin tetrapeptide analogues: role of lipophilicity vs structural flexibility.
Two dermorphin analogues having an almost identical structure but different structural flexibility were compared for opioid activity. In 1 the aromatic side chains were incorporated into a lactam structure, while in 2 N-amide alkylation was retained but the side chains were flexible. Both compounds produced comparable antinociceptive effects in the mouse tail flick test after peripheral administration. This indicates that lipophilicity, rather than side chain flexibility, is the key determinant for blood-CNS barrier penetration.
Ballet
Steven
S
Organic Chemistry Department, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium.
Misicka
Aleksandra
A
Kosson
Piotr
P
Lemieux
Carole
C
Chung
Nga N
NN
Schiller
Peter W
PW
Lipkowski
Andrzej W
AW
Tourwé
Dirk
D
D000818:Animals; D001812:Blood-Brain Barrier; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D018847:Opioid Peptides / Q000493:pharmacokinetics*
D008055:Lipids; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin