MPEP hydrochloride is a highly potent, selective, and non-competitive antagonist of mGlu5 receptor with IC50 of 36 nM, it exhibits no appreciable activity at mGlu1b/2/3/4a/7b/8a/6 receptors. In mice lacking Fmr1, MPEP improves maze learning and PSD-95 deficiencies. MPEP does not cause harm to the adult retrosplenial cortex, unlike the NMDA antagonist MK-801, where it is unable to induce heat shock protein 70 (Hsp70). Additionally, as demonstrated by caspase 3 expression, MPEP does not induce apoptosis in cortical areas during perinatal stages to the same degree as MK-801. The anxiolytic and antidepressant effects of MPEP have been linked to new cellular targets by these data, which also show that MPEP does not have the cortical neurotoxicity linked to psychotomimetic side effects that is present in MK-801. The medication MPEP may be used as an antidepressant or anxiolytic.

Physicochemical Properties

Molecular Formula	C14H12CLN
Molecular Weight	229.70478
Exact Mass	229.065
Elemental Analysis	C, 73.20; H, 5.27; Cl, 15.43; N, 6.10
CAS #	219911-35-0
Related CAS #	MPEP; 96206-92-7
PubChem CID	9794588
Appearance	Yellow solid powder
Density	1.1g/cm3
Boiling Point	336.3ºC at 760mmHg
Flash Point	144.8ºC
Vapour Pressure	0.000221mmHg at 25°C
Index of Refraction	1.614
LogP	3.591
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	1
Rotatable Bond Count	2
Heavy Atom Count	16
Complexity	251
Defined Atom Stereocenter Count	0
SMILES	CC1=NC(C#CC2=CC=CC=C2)=CC=C1.[H]Cl
InChi Key	PKDHDJBNEKXCBI-UHFFFAOYSA-N
InChi Code	InChI=1S/C14H11N.ClH/c1-12-6-5-9-14(15-12)11-10-13-7-3-2-4-8-13;/h2-9H,1H3;1H
Chemical Name	2-methyl-6-(2-phenylethynyl)pyridine;hydrochloride
Synonyms	2-methyl-6-(phenylethynyl)-pyridine;MPEP; MPEP HCl; MPEP hydrochloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	mGluR5 ( IC50 = 36 nM )
ln Vitro	In vitro activity: MPEP exhibits neither agonist nor antagonist activity at 100 mM on human mGlu2, -3, -4a, -7b, and -8a receptors, as well as at 10 μM on the human mGlu6 receptor[1].
ln Vivo	MPEP (1-30 mg/kg) causes anxiolytic-like effects in the conflict drinking test, the elevated plus-maze test, and the four-plate test in mice[2]. MPEP (1–20 mg/kg) does reduce the immobility period in mice; however, in a behavioral despair test, it has no effect in rats in a tail suspension test[2]. MPEP (30 mg/kg i.p.) marginally but significantly raises the number of crossings that result in a penalty (by 39%); lower concentrations of the compound (3 and 10 mg/kg) have no effect on this number (F (3,36)=3.240, P<0.05) in the four-plate test[2]. MPEP (1, 10 and 20 mg/kg) significantly reduces the immobility time of mice (by 55% after the highest dose; F(3,28)=15.47, P<0.001) in the tail suspension test. Its effectiveness is comparable to that of imipramine (20 mg/kg), which is the gold standard[2].
Enzyme Assay	MPEP has an IC50 of 36 nM and is a very strong, selective, and non-competitive mGlu5 receptor antagonist. It shows no discernible activity at mGlu1b/2/3/4a/7b/8a/6 receptors.
Cell Assay	In slices of rat neonatal hippocampus, striatum, and cortex but not cerebellum, MPEP inhibits DHPG-stimulated PI hydrolysis with IC50 of 8.0 nM, 20.5 nM, and 17.9 nM, respectively. MPEP activates the orthosteric agonist L-AP4, which is necessary for MPEP to have any effect. MPEP positively modulates hmGluR4 in a recombinant expression system.
Animal Protocol	Suspended in a 1% aqueous solution of Tween 80; 30 mg/kg; i.p. or p.o. administration Male Wistar rats, male Albino Swiss mice, or male C57BL/6J mice subjected to various tests
References	[1]. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a Potent, Selective and Systemically Active mGlu5 Receptor Antagonist. Neuropharmacology. 1999 Oct;38(10):1493-503. [2]. Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol. 2001 Apr;132(7):1423-30.
Additional Infomation	2-methyl-6-(phenylethynyl)pyridine hydrochloride is a hydrochloride salt obtained by reaction of 2-methyl-6-(phenylethynyl)pyridine with one equivalent of hydrochloric acid. Potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype (IC50 = 36 nM) and a positive allosteric modulator at mGlu4 receptors. Centrally active following systemic administration in vivo. Reverses mechanical hyperalgesia in the inflamed rat hind paw. It has a role as a metabotropic glutamate receptor antagonist and an anxiolytic drug. It contains a 2-methyl-6-(phenylethynyl)pyridinium(1+).

Solubility Data

Solubility (In Vitro)

DMSO: >10 mM Water: Ethanol:

Solubility (In Vivo)

Solubility in Formulation 1: 100 mg/mL (435.35 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2% DMSO+30% PEG 300+5% Tween 80: 10 mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.3535 mL	21.7675 mL	43.5350 mL
	5 mM	0.8707 mL	4.3535 mL	8.7070 mL
	10 mM	0.4354 mL	2.1768 mL	4.3535 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.