An enzymatically stable kyotorphin analog induces pain in subattomol doses.

Abstract

Intraplantar injection of the enzymatically stable, N-methylated kyotorphin analog Tyr(NMe)-Arg-OH produced marked and sharp nociceptive flexor responses in a dose-dependent manner. A significant response was observed with this compound at a dose of 0. 01 amol (6000 molecules). Tyr(NMe)-Arg-OH-nociception was completely blocked by the kyotorphin antagonist leucyl-arginine and its enzymatically stable, N-methylated analog, as well as by CP-99994, a specific neurokinin 1 antagonist. These findings suggest that the nociceptive effect produced by Tyr(NMe)-Arg-OH in subattomol doses occurs via specific interaction with the kyotorphin receptor and that the extraordinary potency observed may result from amplification through local substance P release.

• Authors: H Ueda, M Inoue, G Weltrowska, P W Schiller
• Journal: Peptides (Peptides) Vol. 21 Issue 5 Pg. 717-22 (May 2000) ISSN: 0196-9781 [Print] United States
• PMID: 10876055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Endorphins
• Neurokinin-1 Receptor Antagonists
• kyotorphin

Topics

• Analgesics (pharmacology)
• Animals
• Dose-Response Relationship, Drug
• Drug Stability
• Endorphins (antagonists & inhibitors, chemistry, pharmacology)
• Male
• Mice
• Neurokinin-1 Receptor Antagonists
• Pain (chemically induced)