Characterization of the 1H-cyclopentapyrimidine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, and subtype-selective AMPA receptor full agonist with partial desensitization properties.
(S)-CPW399 (2b) is a novel, potent, and subtype-selective AMPA receptor full agonist that, unlike (S)-willardiine and related compounds, in mouse cerebellar granule cells, stimulated an increase in [Ca(2+)](i), and induced neuronal cell death in a time- and concentration-dependent manner. Compound 2b appears to be a weakly desensitizing, full agonist at AMPA receptors and therefore represents a new pharmacological tool to investigate the role of AMPA receptors in excitotoxicity and their molecular mechanisms of desensitization.
Campiani
G
G
Dipartimento Farmaco Chimico Tecnologico (DFCT), Universita' degli Studi di Siena, via Aldo Moro, 53100 Siena, Italy. campiani@unisi.it
Morelli
E
E
Nacci
V
V
Fattorusso
C
C
Ramunno
A
A
Novellino
E
E
Greenwood
J
J
Liljefors
T
T
Griffiths
R
R
Sinclair
C
C
Reavy
H
H
Kristensen
A S
AS
Pickering
D S
DS
Schousboe
A
A
Cagnotto
A
A
Fumagalli
E
E
Mennini
T
T
D000409:Alanine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009865:Oocytes / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D018091:Receptors, AMPA / Q000819:agonists* / Q000378:metabolism / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D013237:Stereoisomerism; D014982:Xenopus laevis
C443679:CPW 399; D018690:Excitatory Amino Acid Agonists; D008024:Ligands; D011743:Pyrimidines; D011744:Pyrimidinones; D018091:Receptors, AMPA; D011994:Recombinant Proteins; D000409:Alanine