The highly rigid and conformationally extended 2-amino-4-phosphonobutanoic acid (AP4) analogue (RS-1-amino-3-(phosphonomethylene)-cyclobutane-1-carboxylic acid (cyclobutylene AP5) was synthesized and found to inhibit evoked responses in the rat lateral perforant path (LPP) with an IC50 of 41 (±1.5 S.E.M.) μM and the medial perforant pathway with an IC50 of 218 (±3.7 S.E.M.) μM. Furthermore, paired pulse potentiation experiments suggest that cyclobutylene AP5 acts, in part, at a presynaptic site in the LPP. Thus, cyclobutylene AP5 appears to act in a similar manner to l-AP4 in the perforant pathway. These data support the hypothesis that l-AP4 assumes an extended conformation at the l-AP4 receptor of the LPP.
- Lateral perforant path
- l-2-Amino-4-phosphonobutanoic acid
- l-2-Amino-4-phosphonobutanoic acid receptor