A 841720

A 841720 is a novel non-competitive antagonist of metabotropic glutamate receptor 1 (mGluR1), with an IC50 value of 10.7 nM to 10 µM L-glutamate-induced calcium release at human mGluR1 receptors [1].

Glutamate as the major excitatory neurotransmitter in the central nervous system functions through two types of receptors, ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). MGluRs includes group I mGluRs (mGluR1 and mGluR5 receptors), group II (mGluR2 and mGluR3 receptors) and group III (mGluR4, 6, 7, 8 receptors) [1].

In cells, agonist-induced calcium release was concentration-dependently inhibited by A 841720 in a human mGluR5 receptor FLIPR functional assay. But the IC50 value was just 343 nM. In cells expressing recombinant mGluR5 receptors, A 841720 did not block agonist-induced response. In the human mGluR1 receptor FLIPR assay, the log concentration-response curve was shifted by A 841720 at 10 nM to the right. A 841720 at increasing concentrations profoundly reduced the amplitude of L-quisqualate-evoked calcium release. A 841720 at 30 nM reduced the maximal agonist-induced response by 38%. L-quisqualate-induced response was completely abolished by A 841720 at 100 nM [1].

In a water maze test, all rats gradually learned to locate the submerged platform. Treatment with A 841720 significantly slowered rats to find the platform than vehicle control rats. Rats treated with A 841720 at both 30 and 100 µmol/kg doses not only significantly traveled longer distance to find the hidden platform, but also significantly spent longer time to reach the platform [1].

Reference:
[1].  El-Kouhen O, Lehto SG, Pan JB, et al. Blockade of mGluR1 receptor results in analgesia and disruption of motor and cognitive performances: effects of A-841720, a novel non-competitive mGluR1 receptor antagonist. British journal of pharmacology, 2006, 149(6): 761-774.