GLYCOPEPTIDE ENKEPHALIN ANALOGS PRODUCE ANALGESIA IN MICE - EVIDENCE FOR PENETRATION OF THE BLOOD-BRAIN-BARRIER

Most peptides have not proved useful as neuroactive drugs because they are blocked by the blood-brain barrier and do not reach their recepto rs within the brain. Intraperitoneally administered L-serinyl beta-D-g lucoside analogues of [Met(5)]enkephalin (glycopeptides) have been sho wn to be transported across the blood-brain barrier to bind with targe ted mu- and delta-opioid receptors in the mouse brain. The opioid natu re of the binding has been demonstrated with intracerebroventricularly administered naloxone. Paradoxically, glucosylation decreases the lip ophilicity of the peptides while promoting transport across the lipoph ilic endothelial layer. It is suggested that glucose transporter GLUT- 1 is responsible for the transport of the peptide message. Profound an d long-lasting analgesia has been observed in mice (tail-flick and hot -plate assays) with two of the glycopeptide analogues when administere d intraperitoneally.