Phenylglycine derivatives as antagonists of group III metabotropic glutamate receptors expressed on neonatal rat primary afferent terminals

Abstract
Three novel phenylglycine analogues; (RS)‐α‐methyl‐3‐chloro‐4‐phosphonophenylglycine (UBP1110), (RS)‐α‐methyl‐3‐methoxy‐4‐phosphonophenylglycine (UBP1111) and (RS)‐α‐methyl‐3‐methyl‐4‐phosphonophenylglycine (UBP1112) antagonised the depression of the fast component of the dorsal root‐evoked ventral root potential induced by (S)‐AP4 with apparentKDvalues of: 7.4±2.3, 5.4±0.6 and 5.1±0.3μM(alln=3), respectively. A Schild analysis of the antagonism of (S)‐AP4 induced depression of synaptic transmission by UBP1112 revealed a pA2value of 5.3 and a slope of 0.81±0.26 (n=9). None of the phenylglycines tested were potent antagonists of responses mediated by group II mGlu receptors (apparentKDvalues >480μM). UBP1112 when tested at a concentration of 1 mMhad little or no activity on (S)‐3,5‐DHPG‐, NMDA‐, AMPA‐ or kainate‐induced responses on motoneurones. British Journal of Pharmacology(2003)139, 1523–1531. doi:10.1038/sj.bjp.0705377