Heterocyclic GABA analogues. Displacement of radiolabelled 3H-GABA from rat brain membrane preparations.
2,5-Dimethyl-1H-pyrrol-1-yl-butanoic acid (I) and 2,5-diethyl-1H-pyrrol-1-yl-butanoic acid (V) were synthesised as non basic analogues of 4-aminobutanoic acid (GABA) to investigate the influence of the pKa of the 4-nitrogen on the in vitro binding to GABA receptors. (I) displaced 3H-GABA from specific binding sites of synaptosomal membrane preparations from rat cerebellum with an IC50 of 0.5 microM and (V) with an IC50 of 0.4 microM. (I) was inactive in vivo in the bicuculline anticonvulsant test (mice i.p.). The authors conclude that a basic nitrogen is not necessary for the binding to the GABAergic receptors although the ensuing complex is likely to be pharmacologically ineffective.
Varasi
M
M
Lepetit Research Laboratories, Milan, Italy.
Tarzia
G
G
Luzzani
F
F
Gallico
L
L
Barone
D
D
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis; D001640:Bicuculline; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D013045:Species Specificity; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000927:Anticonvulsants; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline