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

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 apparent K D values of: 7.4±2.3, 5.4±0.6 and 5.1±0.3 μ M (all n =3), respectively. A Schild analysis of the antagonism of ( S )‐AP4 induced depression of synaptic transmission by UBP1112 revealed a p A 2 value 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 (apparent K D values >480 μ M ). UBP1112 when tested at a concentration of 1 m M had 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