Thioether analogues of baclofen, phaclofen and saclofen.
Analogues of baclofen, phaclofen and saclofen, incorporating a sulfur atom within the methylene chain, have been tested against responses induced by baclofen for activity at gamma-aminobutyric acid-B (GABAB) receptor sites, using a number of preparations including the guinea-pig isolated ileum and vas deferens, rat brain cortical slices and displacement of (-)-[3H]baclofen in rat cerebellar membranes. Results indicate that 2-([2-amino-1-(4-chlorophenyl)ethyl]thio)ethanephosphonic acid 2d is the most active of the new compounds. 2d is some 2-5 times weaker than phaclofen as a GABAB antagonist and approximately half as potent as phaclofen as an inhibitor of GABAB binding.
Allan
R D
RD
Department of Pharmacology, University of Sydney, N.S.W., Australia.
Drew
C A
CA
Ong
J
J
Tran
H W
HW
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001667:Binding, Competitive; D002531:Cerebellum / Q000378:metabolism*; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D014649:Vas Deferens / Q000378:metabolism*
D011963:Receptors, GABA-A; C052329:phaclofen; D001418:Baclofen