ec50: 500 nmlu af21934 is a positive allosteric modulator of mglu4 receptors.the mglu4 receptor subtype of the group iii mglu is mainly a presynaptic auto- or hetero-receptor. its stimulation results in an inhibition of glutamatergic or gabaergic transmission and release
lu af21934 has been identified as a brain-penetrating positive allosteric modulator of mglu4 receptors. in broad in-vitro screens, lu af21934 could potentiate the glutamate response at the mglu4 receptor with an emax=120% and a glutamate fold-shift fs=5. lu af21934 did not showed any significant affinity for 70 gpcrs at 10 μm, but acted as a weak positive allosteric modulator of mglu6 receptor, as well as an antagonist of adenosine a2a and 5-ht2b receptors [1].
in rats, harmaline triggered tremor as manifested by an increase in the power within 9-15hz band and in the tremor index. harmaline also induced a biphasic effect on mobility, initially inhibiting the exploratory locomotor activity of rats, followed by an increase in their basic activity. lu af21934 at 0.5-5 mg/kg sc did not influence tremor but at doses of 0.5 and 2.5 mg/kg reversed harmaline-induced hyperactivity. mglu4 mrna expression was found to be high in the cerebellar cortex and low in the inferior olive [1].
| mGlu4 Receptor 500 nM (EC 50 ) |
[1] ossowska k,wardas j,berghauzen-maciejewska k,et al. lu af21934, a positive allosteric modulator of mglu4 receptors, reduces the harmaline-induced hyperactivity but not tremor in rats. neuropharmacology.2014 aug;83:28-35.
