Antagonist activity of methyl-substituted analogues of 2-amino-4-phosphonobutanoic acid in the hippocampal slice.
Four monomethyl-substituted analogues of 2-amino-4-phosphonobutanoic acid (APB), an antagonist of excitatory pathways in the central nervous system, were prepared in order to investigate the steric requirements of the APB receptor. Methyl groups were incorporated at the amino, alpha-, beta-, and gamma-positions. The beta- and gamma-methyl-substituted analogues of APB were found to be moderately potent antagonists in excitatory synapses of the hippocampal perforant path, as judged by extracellular recording techniques, while the N- and alpha-methyl-substituted analogues had much lower potencies. All of these APB analogues had very low potencies in the Schaffer collateral pathway. The APB receptors in the perforant path displayed more tolerance of methyl-substitution at the beta- and gamma-positions of APB than at the amino or alpha-positions in this system.
Crooks
S L
SL
Freund
R K
RK
Halsrud
D A
DA
Koerner
J F
JF
Johnson
R L
RL
D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects
D000613:Aminobutyrates; C012729:2-amino-4-phosphonobutyric acid