Spinal actions of GR73632, a novel tachykinin NK1 receptor agonist.
Behavioral characterization of GR73632, a newly synthesized tachykinin NK1 receptor agonist, was examined in mice. Intrathecal (IT) injection of GR73632 in the spinal subarachnoid space of mice elicited a dose-dependent behavioral syndrome, consisting of scratching, biting and licking. The time course of the response to GR73632 was almost similar to that of substance P. GR73632 evoked much more licking and biting than did substance P, that in turn caused less scratching. GR73632 was approximately 200-fold more potent than substance P in inducing the characteristic behavioral response. The GR73632-induced behavioral response was inhibited by IT co-administration of CP-96,345, a non-peptide NK1 receptor antagonist, but not its inactive enantiomer CP-96,344. CP-96,345, co-injected IT with substance P, also inhibited the behavioral response to substance P. These results demonstrate that the scratching, biting and licking response induced by IT GR73632 may be mediated by the NK1 receptor in the spinal cord. These findings suggest that GR73632 may be useful as a tachykinin NK1 receptor agonist and also for evaluating spinal pharmacological activities of NK1 receptor antagonists.
Sakurada
C
C
Department of Biochemistry, Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan.
Watanabe
C
C
Inoue
M
M
Tan-No
K
K
Ando
R
R
Kisara
K
K
Sakurada
T
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology; D004347:Drug Interactions; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000819:agonists*; D013116:Spinal Cord / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology
D001713:Biphenyl Compounds; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; C068032:GR 73632; D013373:Substance P; C066892:CP 96345