A potent nonpeptide antagonist of the substance P (NK1) receptor.
CP-96,345 [(2S, 3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)- methyl]-1-azabicyclo[2.2.2]octan-3-amine] is a potent nonpeptide antagonist of the substance P (NK1) receptor. CP-96,345 inhibited 3H-labeled substance P binding and was a classical competitive antagonist in the NK1 monoreceptor dog carotid artery preparation. CP-96,345 inhibited substance P-induced salivation in the rat, a classical in vivo bioassay, but did not inhibit NK2, NK3, or numerous other receptors; it is thus a selective NK1 antagonist. This compound may prove to be a powerful tool for investigation of the physiological properties of substance P and exploration of its role in diseases.
Snider
R M
RM
Department of Exploratory Medicinal Chemistry, Central Research Division, Pfizer Inc., Groton, CT 06340.
Constantine
J W
JW
Lowe
J A
JA
Longo
K P
KP
Lebel
W S
WS
Woody
H A
HA
Drozda
S E
SE
Desai
M C
MC
Vinick
F J
FJ
Spencer
R W
RW
D000818:Animals; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects; D002417:Cattle; D004285:Dogs; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D012472:Salivation / Q000187:drug effects; D013237:Stereoisomerism; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology
D001713:Biphenyl Compounds; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; C066892:CP 96345