Cyclic analogues of Tyr-W-MIF-1 with prolonged analgesic activity and potency comparable to DAMGO and morphine.
Two cyclic analogues of the brain peptide Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) were synthesized and tested for analgesic activity in the rat tail flick test after intracerebroventricular (ICV) injection. The analogues were about 200-fold more potent than the parent peptide. Analgesia was dose dependent, and at 1 microgram the two analogues, the mu-selective enkephalin analogue DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol), and morphine, all produced analgesia lasting between 40 and 60 min. Analgesia of longer duration was evident at higher doses of the analogues and lasted more than 6 h after 100 micrograms, the highest dose tested. The results show that peptide analogues based on the structure of the endogenously occurring Tyr-W-MIF-1 can produce potent and long-lasting effects on nociception.
Zadina
J E
JE
VA Medical Center, New Orleans, LA.
Kastin
A J
AJ
Hackler
L
L
Chang
S L
SL
D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D010456:Peptides, Cyclic; C090788:tyrosyl-cyclo(lysyl-tryptophyl-glycyl); C090787:tyrosyl-cyclo(ornithyl-tryptophyl-glycyl); D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C077532:tyrosyl-prolyl-tryptophyl-glycinamide; D009020:Morphine; D009075:MSH Release-Inhibiting Hormone