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Antinociceptive activity of peptides related to interleukin-1 beta-(193-195), Lys-Pro-Thr.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 1994 Jun 02; Vol. 258 (1-2), pp. 131-8. - Publication Year :
- 1994
-
Abstract
- A series of closely related peptide analogues of Lys-Pro-Thr [(interleukin-1 beta-(193-195)] have been investigated in two models of antinociception in mice (acetic acid-induced abdominal constrictions and formalin tests) and compared with morphine, aspirin and indomethacin. Formalin-induced nociceptive responses in the mouse showed early (0-5 min) and late (15-30 min) phases of peak activity. Lys-D-Pro, Lys-D-Pro-Thr, Lys-D-Pro-Arg, Lys-D-Pro-Val, morphine and aspirin, were antinociceptive in both phases after intraperitoneal (i.p.) and oral (p.o.) administrations. Lys-D-Pro-Leu inhibited the early phase response only after i.p. injection. Lys-D-Pro-Val-NH2, Lys-D-Pro-Gln, Lys-D-Pro-Tyr, Lys-D-Pro-Asn, Asp-Lys-D-Pro-Val and indomethacin were active only against the late phase (ED50 values of 64, 32, 44, 94, 67 and 25 mg/kg i.p., respectively). Several of the peptides showed good bio-availability, e.g. Lys-D-Pro-Asn (ED50: 10 mg/kg i.p.; 11.4 mg/kg p.o.) in the abdominal constrictions test, where two modes of action were apparent, non-opioid and opioid; non-opioid (naloxone-insensitive antinociception) mechanisms were illustrated by Lys-D-Pro-Thr and Lys-D-Pro-Asn; opioid (naloxone-sensitive antinociception) mechanisms by Lys-D-Pro-Val and Lys-D-Pro-Leu. These data identify orally active antinociceptive peptides in both antinociceptive tests with varied relative potency profiles to morphine, indomethacin and aspirin in the mouse formalin test.
- Subjects :
- Abdomen
Administration, Oral
Amino Acid Sequence
Animals
Dose-Response Relationship, Drug
Injections, Intraperitoneal
Interleukin-1 chemistry
Interleukin-1beta
Male
Mice
Molecular Sequence Data
Muscle Contraction drug effects
Muscle, Smooth drug effects
Pain Measurement
Peptide Fragments chemistry
Analgesics pharmacology
Interleukin-1 pharmacology
Peptide Fragments pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 258
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 7925591
- Full Text :
- https://doi.org/10.1016/0014-2999(94)90065-5