MPEP is a potent, selective, noncompetitive, orally active and systemically active mGlu5 receptor antagonist, with an IC50 of 36 nM for completely inhibiting quisqualate-stimulated phosphoinositide (PI) hydrolysis. MPEP does not show agonist or antagonist activity at 100 mM on human mGlu2, -3, -4a, -7b, and -8a receptors nor at 10 μM on the human mGlu6 receptor[3]. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats[4]. MPEP (10 and 30 mg/kg) significantly enhanced both the sedative and hypnotic effects of ethanol[5].
MPEP 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Dopamine neurons
300 nM
Block mGluR5 receptors to prevent cocaine-induced reduction in mGluR1 currents
Neuropsychopharmacology. 2015 Sep;40(10):2418-24
MN9D cells
100 μM
30 min
Inhibited rotenone-induced JNK phosphorylation, protected cells from apoptosis
Neurotherapeutics. 2019 Jul;16(3):761-783
C6 astroglial cells
10 μM
25 min
Blocked mGluR5 activity, inhibited DHPG-induced AKT and ERK1/2 phosphorylation
Neurotherapeutics. 2019 Jul;16(3):761-783
Hippocampal organotypic slice cultures (HOCS)
36 nM
21–45 days
MPEP significantly ameliorated the neurodegeneration triggered by prion infection
PLoS Pathog. 2017 Nov 27;13(11):e1006733
Cerebellar organotypic slice cultures (COCS)
10 nM
21–45 days
MPEP significantly ameliorated the neurodegeneration triggered by prion infection
PLoS Pathog. 2017 Nov 27;13(11):e1006733
Jurkat E6.1 cells
20 μM
20 minutes
To investigate the effect of MPEP on mGluR5 activity in Jurkat cells, results showed that MPEP pretreatment decreased RANTES release.
Transl Psychiatry. 2018 May 30;8(1):110
MPEP 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Wild-type and p11 knockout mice
Intraperitoneal injection
3 mg/kg
Single dose, behavioral tests conducted 30 min or 24 hr after administration
To investigate the antidepressant-like behavioral effects of MPEP, it was found that MPEP exhibited antidepressant-like behaviors in wild-type mice, but this effect was abolished in p11 knockout mice.
Mol Psychiatry. 2015 Dec;20(12):1546-56
Mice
Neuropathic pain model (SNI model)
Subcutaneous injection
1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg
Single or multiple doses, lasting for 8 days
To evaluate the analgesic effects and side effects of MPEP in a neuropathic pain model. Results showed that MPEP partially alleviated mechanical hyperalgesia early (10 days) but had reduced efficacy late (30 days). Additionally, MPEP did not exhibit the side effects of traditional opioids, such as respiratory depression and locomotor behavior changes.
Pain. 2020 Sep 1;161(9):2041-2057
Wistar rats
Chronic migraine rat model
Intracerebroventricular administration
0.2 μg, 2 μg, 5 μg/5 μL
Single administration
MPEP alleviated the allodynia and reduced the expression of CGRP, pCREB-S133, c-Fos, PSD, Syp and Syt-1 and synaptic transmission in CM rats. Moreover, the administration of MPEP inhibited the upregulation of PKC and pNR2B-Y1472.
J Headache Pain. 2020 Dec 4;21(1):139
Mice
Intraperitoneal injection
30 mg/kg
Single injection
Block mGluR5 receptors to prevent cocaine-induced reduction in mGluR1 currents
Neuropsychopharmacology. 2015 Sep;40(10):2418-24
ICR-CD1 mice
Neuropathic pain model
Intrathecal injection
1, 3, 10 nmol
30-minute intervals
To evaluate the synergistic effects of MPEP with morphine-like drugs, results showed that MPEP combined with oxymorphone or oxymorphamine had synergistic analgesic effects.
Pain. 2017 Dec;158(12):2431-2441
Sprague-Dawley rats
Rotenone-induced PD model
Intraperitoneal injection
1.5 mg/kg/day
For continuous 3 weeks
MPEP attenuated behavioral deficits and dopaminergic neuronal death, while CAL knockdown weakened the protective effect of MPEP
Neurotherapeutics. 2019 Jul;16(3):761-783
C57BL/6J male mice
Prion-infected mouse model
Oral
30 mg/kg/day
Daily until the end of the experiment
MPEP significantly delayed the onset of motor deficits and moderately prolonged survival of prion-infected mice
PLoS Pathog. 2017 Nov 27;13(11):e1006733
Cynomolgus monkeys (Macaca fascicularis)
MPTP-induced Parkinson's disease model
Oral
10 mg/kg
Once daily for one month
MPEP blockade of metabotropic glutamate receptor 5 prevents L-Dopa-induced dyskinesias and is associated with reduced inflammation in the brain of Parkinsonian monkeys. MPEP co-treatment with L-Dopa significantly reduced the development of dyskinesias and decreased levels of inflammatory markers (Iba1, CD68, and GFAP) in the basal ganglia.
Mexico
... 展开 >> Asociacion Mexicana para la Salud Sexual, A.C.
Mexico City, Mexico D.F., Mexico, 14000
Centro Especializado en Urología y Andrología del Hospital Star Médica
Mexico City, Mexico D.F, Mexico, 06700 收起 <<
Mexico
... 展开 >> Asociacion Mexicana para la Salud Sexual, A.C.
Mexico City, Mexico D.F., Mexico, 14000
Centro Especializado en Urología y Andrología del Hospital Star Médica
Mexico City, Mexico D.F, Mexico, 06700 收起 <<
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