Antinociceptive activity of NK1 receptor antagonists: non‐specific effects of racemic RP67580
1 Release of substance P in the dorsal horn is considered a primary event in the perception of pain. The profile of racemic RP67580, a non‐peptide antagonist at the NK1 (substance P) receptor, was examined in a range of antinociception tests on rodents. 2 At doses up to 30 mg kg−1, s.c. racemic RP67...
Saved in:
Published in | British journal of pharmacology Vol. 110; no. 4; pp. 1607 - 1613 |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.12.1993
Nature Publishing Nature Publishing Group |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 1
Release of substance P in the dorsal horn is considered a primary event in the perception of pain. The profile of racemic RP67580, a non‐peptide antagonist at the NK1 (substance P) receptor, was examined in a range of antinociception tests on rodents.
2
At doses up to 30 mg kg−1, s.c. racemic RP67580 exhibited antinociceptive activity in writhing and formalin paw tests in mice and gerbils. Acetic acid induced writhing and the licking response to formalin were reduced to 40–50% of the level observed in vehicle‐treated animals (P < 0.05). However, this agent was not active in mouse tail flick, rat paw pressure or rat and guinea‐pig formalin paw tests.
3
Like racemic RP67580, the calcium channel blockers nifedipine (30 mg kg−1, i.p.) and verapamil (10 or 20 mg kg−1, s.c.) inhibited the response to formalin by approximately 60% in gerbils (P < 0.05 compared with vehicle‐treated animals).
4
Evidence for calcium channel antagonist activity of RP67580 was obtained in vitro. Racemic RP67580 inhibited calcium entry into depolarized strips of guinea‐pig ileum longitudinal muscle myenteric plexus (apparent KB = 587 ± 115 nm), inhibited [3H]‐diltiazem binding to rabbit skeletal membranes (IC50 = 298 nm) and depressed high threshold calcium currents in neurones cultured from rat cortex (10% inhibition at 10 μm).
5
These findings indicate that the acute antinociceptive effects of RP67580 may not be attributable to a specific interaction with NK1 receptors and may be mediated via calcium channel blockade. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0007-1188 1476-5381 |
DOI: | 10.1111/j.1476-5381.1993.tb14008.x |