Abstract:
:Our understanding of the role GABA(C) receptors play in the central nervous system is limited due to a lack of specific ligands. Here we describe the pharmacological effects of (+/-)-cis-3- and (+/-)-trans-3-(aminocyclopentyl)methylphosphinic acids ((+/-)-cis- and (+/-)-trans-3-ACPMPA) as novel ligands for the GABA(C) receptor showing little activity at GABA(A) or GABA(B) receptors. (+/-)-cis-3-ACPMPA has similar potency to (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) at human recombinant rho1 (K(B)=1.0+/-0.2microM) and rat rho3 (K(B)=5.4+/-0.8microM) but is 15 times more potent than TPMPA on human recombinant rho2 (K(B)=1.0+/-0.3microM) GABA(C) receptors expressed in Xenopus oocytes. (+/-)-cis- and (+/-)-trans-3-ACPMPA are novel lead compounds for developing into more potent and selective GABA(C) receptor antagonists with increased lipophilicity for in vivo studies.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Chebib M,Hanrahan JR,Kumar RJ,Mewett KN,Morriss G,Wooller S,Johnston GAdoi
10.1016/j.neuropharm.2006.09.014subject
Has Abstractpub_date
2007-03-01 00:00:00pages
779-87issue
3eissn
0028-3908issn
1873-7064pii
S0028-3908(06)00341-8journal_volume
52pub_type
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