A novel antagonist, phenylbenzene ω‐phosphono‐α‐amino acid, for strychnine‐sensitive glycine receptors in the rat spinal cord

1 3‐[2′‐Phosphonomethyl[1,1′‐biphenyl]‐3‐yl]alanine (PMBA) is a novel glycine antagonist at strychnine‐sensitive receptors. The chemical structure of PMBA, possessing both a glycine moiety and a phosphono group, is quite different from that of strychnine. 2 In the spinal motoneurone of newborn rats, glycine (100 μm‐1 mM) induced depolarizing responses in a concentration‐dependent manner. PMBA effectively inhibited depolarizing responses to glycine and other agonists, such as taurine and β‐alanine. The dose‐response curves for glycine were shifted to the right in an almost parallel manner (pA 2 value: 5.30 ± 0.23, n = 5) by PMBA which was about 60 times less potent than strychnine (pA 2 value: 7.08 ± 0.21, n = 5) as a glycine antagonist. 3 PMBA (1 − 100 μ m ) did not interact with modulatory glycine sites on N‐methyl‐D‐aspartate (NMDA) receptors, which suggests a high selectivity of PMBA for strychnine‐sensitive glycine receptors. At considerably high concentrations (0.1 mM‐1 mM), PMBA depressed responses to GABA (pA 2 value: 3.57 ± 0.24, n = 3). 4 PMBA inhibited the binding of [ 3 H]‐strychnine to synaptosomes from adult rat spinal cords; the IC 50 values of PMBA, glycine and strychnine were 8 ± 2, 9 ± 3 and 0.08 ± 0.04 μm, respectively ( n = 5) for [ 3 H]‐strychnine (4.8 nM). 5 PMBA is a central excitant drug with relatively high potency and selectivity and should be useful as a pharmacological probe for analysing the mechanisms underlying physiological functions of glycine receptors.