Comparison of antagonistic effects of sendide and CP-96,345 on a spinally mediated behavioural response in mice.
Intrathecal administration of the tachykinin NK1 receptor agonists, substance P, physalaemin, septide and [Sar9, Met(O2)11]substance P, elicited a characteristic behavioural response consisting of scratching, biting and licking in mice. The behavioural response induced by substance P was significantly inhibited by simultaneous intrathecal injection of a tachykinin NK1 receptor antagonist, [Tyr6,D-Phe7,D-His9]substance P-(6-11) (sendide), and a non-peptide antagonist, [(2S,3S)-cis-2-(di-phenylmethyl)-N-[(2- methoxyphenyl)-methyl]-1-azabicyclo[2.2.2]octan-3-amine](CP-96,345). The duration of the antagonistic effect of sendide was similar to that of CP-96,345. The antagonistic effect of sendide on the response induced by tachykinin NK1 receptor agonists was approximately 1000 times more potent than that of CP-96,345. Neither antagonist inhibited neurokinin A-, D-septide-, neurokinin B- and eledoisin-induced scratching, biting and licking responses. Sendide was without effect on motor performance as measured by the rotarod test, while motor incoordination was elicited only 2 min after intrathecal injection of CP-96,345. These results indicate that sendide and CP-96,345 are selective antagonists of tachykinin NK1 receptors with a long duration of action.
Sakurada
T
T
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Manome
Y
Y
Katsumata
K
K
Tan-No
K
K
Sakurada
S
S
Ohba
M
M
Kisara
K
K
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007267:Injections; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D018041:Receptors, Neurokinin-2 / Q000819:agonists; D018042:Receptors, Neurokinin-3 / Q000819:agonists; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013346:Subarachnoid Space; D013373:Substance P / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000700:Analgesics; D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D013373:Substance P; C032292:substance P (6-11); D011761:Pyrrolidonecarboxylic Acid; C066892:CP 96345