Ethers of 3-hydroxyphenylacetic acid as selective gamma-hydroxybutyric acid receptor ligands.
Gamma-hydroxybutyric acid (GHB) is a drug of abuse, a therapeutic, and purportedly a neurotransmitter with a complex mechanism of action in vivo due to direct actions at GABA(B) as well as GHB receptors and because of its metabolism to GABA. Herein, we describe 3-ethers of 3-hydroxyphenylacetic acid, which have relatively high affinity at GHB sites, no significant affinity at GABA receptors, and would not be expected to be rapidly metabolized to GABAergic ligands. The selectivity of these compounds (UMB108, UMB109, and UMB119) could prove to be useful for studying the biology of GHB receptors, free from GABAergic effects.
Chen
Weibin
W
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Room 637, Baltimore, MD 21201, USA.
Wu
Huifang
H
Hernandez
R Jason
RJ
Mehta
Ashok K
AK
Ticku
Maharaj K
MK
France
Charles P
CP
Coop
Andrew
A
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002531:Cerebellum / Q000166:cytology; D002540:Cerebral Cortex / Q000166:cytology; D004987:Ethers; D020128:Inhibitory Concentration 50; D008024:Ligands; D010648:Phenylacetates / Q000138:chemical synthesis / Q000737:chemistry*; D011869:Radioligand Assay; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry*; D013329:Structure-Activity Relationship
C026245:3-hydroxyphenylacetate; C039403:4-hydroxybutyric acid receptor; D004987:Ethers; D008024:Ligands; D010648:Phenylacetates; D011956:Receptors, Cell Surface