219911-35-0 Usage
Description
MPEP HYDROCHLORIDE, also known as 2-Methyl-6-(phenylethynyl)pyridine hydrochloride, is a potent and highly selective non-competitive antagonist of the metabotropic glutamate receptor 5 (mGlu5) subtype with an IC50 of 36 nM. It also acts as a positive allosteric modulator at mGlu4 receptors. MPEP HYDROCHLORIDE is centrally active following systemic administration in vivo and has the ability to reverse mechanical hyperalgesia in the inflamed rat hind paw.
Uses
Used in Pharmaceutical Industry:
MPEP HYDROCHLORIDE is used as a research compound for the development of potential therapeutic agents targeting the mGlu5 and mGlu4 receptors. Its high selectivity and potency make it a valuable tool in studying the role of these receptors in various neurological and psychiatric disorders.
Used in Neuroscience Research:
MPEP HYDROCHLORIDE is used as a research tool in neuroscience to investigate the function and modulation of mGlu5 and mGlu4 receptors. This helps researchers understand the underlying mechanisms of related neurological conditions and develop targeted therapies.
Used in Preclinical Models:
MPEP HYDROCHLORIDE is used in preclinical models to study its anxiolytic and antidepressant properties, as well as its potential applicability in treating conditions such as schizophrenia, epilepsy, ischemia, pain, anxiety, and depression. Its effects on rodent models of anxiety and depression have been observed at doses of 1-30 mg/kg.
Used in Drug Discovery:
MPEP HYDROCHLORIDE is used in drug discovery processes to identify and optimize new compounds with similar or improved pharmacological properties. This can lead to the development of more effective and safer treatments for various disorders associated with the dysregulation of mGlu5 and mGlu4 receptors.
Biochem/physiol Actions
GRIN2B (glutamate ionotropic receptor NMDA type subunit 2B) plays an important role in the growth of neurons and is highly essential for learning and memory. GRIN2B mutation is associated with neuropsychiatric and developmental disorders like schizophrenia, Parkinson′s disease and bipolar disorder. MPEP (2-methyl-6-(phenylethynyl)pyridine?hydrochloride) is used to treat Alzheimer′s disease (AD).
in vitro
in recombinant expressed cells human mglu5a receptor, mpep inhibited quisqualate-stimulated phosphoinositide hydrolysis completely with an ic50 value of 36 nm whereas with no agonist or antagonist activities at cells expressing the human mglu1b receptor. mpep did not show agonist or antagonist activity on human mglu2, -3, -4a, -7b, and -8a receptors [1].
in vivo
in rat neonatal brain slices, mpep inhibited dhpg-stimulated phosphoinositide hydrolysis with a potency and selectivity similar to that observed on human mglu receptors. moreover, in extracellular recordings in the hippocampus ca1 area of anesthetized rats, the microiontophoretic application of dhpg induced neuronal firing that was blocked when mpep was administered [1].
IC 50
36 nm
References
1) Gasparini et al. (1999) 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective, and systemically active mGlu5 receptor antagonist; Neuropharmacology 38 1493
2) Mathiesen et al. (2003) Positive allosteric modulation of the human metabotropic glutamate receptor 4(hmGlu4) by SIB-1893 and MPEP; Br. J . Pharmacol. 138 1026
3) Morin et al. (2010) Effect of metabotropic glutamate receptor type 5 antagonists MPEP and MTEP in parkinsonian monkeys; Neuropharmacology 58 981
4) Morin et al. (2013) MPEP, an mGlu5 receptor antagonist, reduces the development of L-DOPA-induced motor complications in de novo parkinsonian monkeys: biochemical correlates; Neuropharmacology 66 355
5) Michalon et al. (2012) Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice; Neuron 74 49
6) Mihov and Hasler (2016) Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window; Int. J. Neuropsychopharmacol. 19 pyw002
Check Digit Verification of cas no
The CAS Registry Mumber 219911-35-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,1,9,9,1 and 1 respectively; the second part has 2 digits, 3 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 219911-35:
(8*2)+(7*1)+(6*9)+(5*9)+(4*1)+(3*1)+(2*3)+(1*5)=140
140 % 10 = 0
So 219911-35-0 is a valid CAS Registry Number.
InChI:InChI=1/C14H11N/c1-12-6-5-9-14(15-12)11-10-13-7-3-2-4-8-13/h2-9H,1H3
