Isoxazolo[3,4-d]pyridazinones positively modulate the metabotropic glutamate subtypes 2 and 4.

ABSTRACT: Isoxazolo[3,4-d] pyridazinones ([3,4-d]s) are selective positive modulators of the metabotropic glutamate receptors (mGluRs) subtypes 2 and 4, with no functional cross reactivity at mGluR_1a, mGLuR₅ or mGluR₈. Modest binding for two of the [3,4-d]s is observed at the allosteric fenobam mGluR₅ site, but not sufficient to translate into a functional effect. The structure activity relationship (SAR) for mGluR₂ and mGluR₄ are distinct: the compounds which select for mGluR₂ all contain fluorine on the N-6 aryl group. Furthermore, the [3,4-d]s in this study showed no significant binding at inhibitory GABA_A, nor excitatory NMDA receptors, and previously we had disclosed that they lack significant activity at th

SUBMITTER: Gates C 

PROVIDER: S-EPMC6675577 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature