9-(Dimethylamino)-3-(hexahydro-1H-azepin-1-yl)pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4(3H)-one

Uses

A 841720 is a potent & non-competitive mGluR-1 antagonist.

Biological Activity

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].

References

[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.