MMPIP

Names

[ Name ]:
MMPIP

[Synonym ]:
S14-1930
Thioperamide
6-(4-Methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[ 4,5-c]pyridin-4(5H)-one

Biological Activity

[Description]:

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].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> mGluR

Research Areas >> Neurological Disease

[Target]

mGlu7

[In Vitro]

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 (IC50=26 nM) [1]. In CHO cells expressing rat mGluR7, MMPIP inhibits L-AP4-induced inhibition of forskolin-stimulated cAMP accumulation (IC0 220 nM)[1]. MMPIP also antagonizes L-AP4-induced inhibition of cAMP accumulation with an IC0 of 610 nM in CHO-human mGluR7/Gα15[1].

[In Vivo]

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, brain 1.75 h) following i.p. administration (10 mg/kg) in mice[2].

[References]

[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 Cieślik, et al. Negative Allosteric Modulators of mGlu 7 Receptor as Putative Antipsychotic Drugs. Front Mol Neurosci. 2018 Sep 20;11:316.

Chemical & Physical Properties

[ Molecular Formula ]:
C₁₉H₁₅N₃O₃

[ Molecular Weight ]:
369.80200

[ Exact Mass ]:
369.08800

[ PSA ]:
70.15000

[ LogP ]:
4.06610

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
P301 + P310

[ Hazard Codes ]:
T+

[ RIDADR ]:
UN 2811 6.1 / PGIII

Articles

AMN082, a metabotropic glutamate receptor 7 allosteric agonist, attenuates locomotor sensitization and cross-sensitization induced by cocaine and morphine in mice.

Prog. Neuropsychopharmacol. Biol. Psychiatry 57 , 166-75, (2014)

Previous studies have indicated that metabotropic glutamate receptors 7 (mGluR7s) are involved in drug addiction. However, the role of these receptors in drug-induced behavioral sensitization is unkno...

MMPIP, an mGluR7-selective negative allosteric modulator, alleviates pain and normalizes affective and cognitive behavior in neuropathic mice.

Pain 156 , 1060-73, (2015)

This study investigated the effects of a single administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridinyl-4-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), a negative allosteric modulator (NAM) of metabot...

In silico molecular comparisons of C. elegans and mammalian pharmacology identify distinct targets that regulate feeding.

PLoS Biol. 11 , e1001712, (2013)

Phenotypic screens can identify molecules that are at once penetrant and active on the integrated circuitry of a whole cell or organism. These advantages are offset by the need to identify the targets...

Related Compounds

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