Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives in three animal models of pain.
Amino acids 5 and 7, two potent and selective competitive GluR5 KA receptor antagonists, exhibited high GluR5 receptor affinity over other glutamate receptors. Their ester prodrugs 6 and 8 were orally active in three models of pain: reversal of formalin-induced paw licking, carrageenan-induced thermal hyperalgesia, and capsaicin-induced mechanical hyperalgesia.
Centro de Investigación Lilly, S. A. Avda. De la Industria 30, 28108-Alcobendas, Madrid, Spain. dominguez_esteban@lilly.com
Esteban
E
Dominguez
Smriti
S
Iyengar
Harlan E
HE
Shannon
David
D
Bleakman
Andrew
A
Alt
Brian M
BM
Arnold
Michael G
MG
Bell
Thomas J
TJ
Bleisch
Jennifer L
JL
Buckmaster
Ana M
AM
Castano
Miriam
M
Del Prado
Ana
A
Escribano
Sandra A
SA
Filla
Ken H
KH
Ho
Kevin J
KJ
Hudziak
Carrie K
CK
Jones
Jose A
JA
Martinez-Perez
Ana
A
Mateo
Brian M
BM
Mathes
Edward L
EL
Mattiuz
Ann Marie L
AM
Ogden
Rosa Maria A
RM
Simmons
Douglas R
DR
Stack
Robert E
RE
Stratford
Mark A
MA
Winter
Zhipei
Z
Wu
Paul L
PL
Ornstein
D000596:Amino Acids / Q000494:pharmacology*; D000700:Analgesics / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000503:physiopathology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D000596:Amino Acids; D000700:Analgesics; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D011994:Recombinant Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid