Discovery of CP-96,345 and its characterization in disease models involving substance P.
Studies with CP-96,345, a potent, selective, orally active, nonpeptide NK1 receptor antagonist, have provided considerable insight into SP pharmacology. Rather than being a primary neurotransmitter, SP prolongs the nociception produced by other neurotransmitters. By controlling endothelial permeability, SP plays a major role in inflammation and inflammatory aspects of asthma, possibly by regulating the access of neutrophils to an inflammatory site. These results indicate potential therapeutic applications for SP antagonists in the treatment of chronic pain, inflammation, and inflammatory aspects of asthma, and signal a new era in the clinical management of these important diseases.
Lowe
J A
JA
Department of Exploratory Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340.
Drozda
S E
SE
Snider
R M
RM
Longo
K P
KP
Zorn
S H
SH
Jackson
E R
ER
Morrone
J
J
McLean
S
S
Bryce
D K
DK
Bordner
J
J
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000378:metabolism* / Q000494:pharmacology*; D004195:Disease Models, Animal; D007249:Inflammation; D010146:Pain / Q000503:physiopathology*; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
D000700:Analgesics; D001713:Biphenyl Compounds; D018041:Receptors, Neurokinin-2; D013373:Substance P; C066892:CP 96345