MMPIP

MMPIP is an allosteric metabotropic glutamate receptor 7 (mGluR7) selective antagonist (KB values 24 -30 nM). MMPIP acts as a pharmacological tool for elucidating the roles of mGluR7 on central nervous system functions. MMPIP alleviates pain and normalizes affective and cognitive behavior in neuropathic mice[1][2].

MMPIP inhibits L-(+)-2-amino-4-phosphonobutyric acid (L-AP4; 0.5 mM)-induced intracellular Ca2+ mobilization in Chinese hamster ovary (CHO) cells coexpressing rat mGluR7 with Gα15 (IC550=26 nM) [1]. In CHO cells expressing rat mGluR7, MMPIP inhibits L-AP4-induced inhibition of forskolin-stimulated cAMP accumulation (IC50 220 nM)[1].MMPIP also antagonizes L-AP4-induced inhibition of cAMP accumulation with an IC50 of 610 nM in CHO-human mGluR7/Gα15[1].

MMPIP (10 mg/kg) attenuates the amplitude of the acoustic startle response and markedly enhances the prepulse-induced inhibition of the acoustic startle response (up to 137% of control)[2].MMPIP (10 mg/kg) rescues the MK-801 (0.1 mg/kg)-induced cognitive impairments, by improving the choice accuracy[2].Zamifenacin exhibits short elimination half-lives (plasma 1.16 h, brain 1.75 h) following i.p. administration (10 mg/kg) in mice[2].

[1]. Gentaroh Suzuki, et al. In vitro pharmacological characterization of novel isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists. J Pharmacol Exp Ther. 2007 Oct;323(1):147-56.
[2]. Paulina Cie?lik, et al. Negative Allosteric Modulators of mGlu 7 Receptor as Putative Antipsychotic Drugs. Front Mol Neurosci. 2018 Sep 20;11:316.