The neurokinin-1 receptor antagonist, sendide, exhibits antinociceptive activity in the formalin test.
Sendide is a selective and extremely potent antagonist of neurokinin-1 (NK1) receptors in the mouse spinal cord. The antinociceptive activities of sendide, an antagonist of NK1 receptors, and its analogue, [D-Trp7]sendide have been examined after intrathecal (i.t.) administrations in the mouse paw formalin test. Intrathecal administration of sendide (in pmol) reduced both the early and late phases of the formalin-induced licking response. [D-Trp7]sendide also produced a significant antinociceptive response with less potent activity than sendide. Even highest doses (4000 pmol sendide and 8000 pmol [D-Trp7]sendide) examined, there was no motor paralysis of the hindlimbs. Intrathecal morphine inhibited both the early and late phases of the formalin-induced licking response in a dose-dependent manner. The results indicate that the antinociceptive effects of sendide and [D-Trp7]sendide may be mediated at NK1 receptors in the formalin-induced nociception.
Sakurada
Tsukasa
T
Department of Pharmacology, Tohoku College of Pharmacy, 4-4-1 Komatsushima, Aoba-ku, Sendai 981 Japan Research Center, Asahi Glass Company, Yokohama 221 Japan.
Katsumata
Kazushige
K
Yogo
Hiromichi
H
Tan-No
Koichi
K
Sakurada
Shinobu
S
Ohba
Masataka
M
Kisara
Kensuke
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005557:Formaldehyde; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000139:chemically induced; D010147:Pain Measurement; D010446:Peptide Fragments / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013373:Substance P / Q000494:pharmacology*
D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; C090191:tryptophyl(7)-sendide; D005557:Formaldehyde; D013373:Substance P; C032292:substance P (6-11); D011761:Pyrrolidonecarboxylic Acid