Uses
ALX 5407 Hydrochloride can be used in the preparation of amino acid derivatives as pharmaceuticals for treatment of neurological and neuropsychiatric disorders.
Uses
ALX 5407 hydrochloride has been used as a glycine transporter (GlyT1) inhibitor to test its effect on inhibitory postsynaptic current and N-methyl-D-aspartate receptor (NMDA)-mediated excitatory postsynaptic currents (EPSCs). It has also been used as a GlyT1 inhibitor to treat developmentally diminished NMDA receptor (Grin1D481N) mice to test its effect on the glycine site function.
Biological Activity
alx 5407 is a potent and selective inhibitor of the hglyt1 glycine transporter. it completely inhibited glycine transport in the glyt1 cells with an ic50 value of 3 nm [1].glyt1 is a family of glycine transporters. transporters terminate the actions of both glycine and glutamate. there are at least three splice variants in the glyt1 family, called 1a, 1b, and 1c. glyt1 is distributed widely throughout the cns, and that distribution correlates better with the localization of n-methyl-d-aspartate (nmda) receptors than with the strychnine-sensitive glycine receptor [1].qt6-1c cells were treated with 50 nm alx 5407, and then were washed four times with hbs. after washing, 90 ?l of hbs was added. the rate at which alx 5407 dissociated from the glyt1c transporter was then measured. a long half-time was found. this indicates the binding of alx 5407 to the glyt1c transporter is essentially irreversible [1].using microdialysis, it was found that in vivo in rat prefrontal cortex (pfc), administration of alx 5407 at a dose of 10 mg/kg, p.o., resulted in an increase of 40% in pfc glycine levels measured 60 to 90 min after drug administration, whereas the lower dose at 1 mg/kg elicited a slight, nonsignificant elevation [1].
Biochem/physiol Actions
ALX-5407 hydrochloride (NFPS hydrochloride) is a selective irreversible inhibitor of the glycine transporter GlyT1 with IC50 values of 3 nM for GlyT1 compared to 100 μM for GlyT2. ALX-5407 hydrochloride showed no activity at the inhibitory glycine receptor or glycine site of the NMDA receptor (IC50 > 100 mM).
in vivo
ALX-5407 hydrochloride (1 and 10 mg/kg; oral administration, once) increases free glycine levels in rat prefrontal cortex[1].
storage
Desiccate at +4°C
References
[1]. atkinson bn, bell sc, de vivo m, et al. alx 5407: a potent, selective inhibitor of the hglyt1 glycine transporter. mol pharmacol, 2001, 60(6):1414-20.
