Description
Glutamate, the major excitatory neurotransmitter in the brain, acts on both ionotropic and metabotropic glutamate receptors. Excessive metabotropic glutamate receptor (mGluR) transmission has been linked to epilepsy, ischemia, pain, anxiety, and depression. Eight subtypes (1-
8) and multiple splice variants of the mGluR have been identified and grouped based on their pharmacological properties. Group I mGluRs (subtypes 1 and 5) activate the phosphatidyl inositol pathway, while Group II (2 and 3) and Group III (4, 6, 7, and 8) inhibit adenylyl cyclase. MTEP is a negative allosteric modulator of the mGlu5a receptor subtype (K
i = 42 nM; IC
50 = 110 nM). MTEP at 0.3 mg/kg produces antidepressant effects in several rodent models of depression. It also demonstrates neuroprotective potential by preventing excitotoxic neuronal damage when administered through either intrahippocampal or intraperitoneal injection. Additionally, MTEP demonstrates an anxiolytic-
like phenotype in rodent models similar to that of benzodiazepines while lacking undesirable sedative and addictive effects.
Uses
MTEP Hydrochloride is a potent mGlu5 receptor antagonist, acting as a negative allosteric modulator.
in vitro
like mpep, mtep showed a nanomolar affinity for mglur5, but seemed to be superior to mpep in term of specificity. mtep did not influence mglur2, mglur7, nmda, ampa or kainate receptors, while inhibited maoa at a concentration three times higher than mpep. moreover, recent study indicated that mtep was five times stronger that mpep as an anxiolytic compound [1].
in vivo
mtep with doses between 0.5 and 3 mg/kg was found to decrease the haloperidol-induced muscle rigidity, which was measured as an increased muscle resistance of the rat hind leg. the longest and strongest effect was observed with the dose of 1 mg/kg. mtep was also found to reduce the haloperidol-induced increase in electromyographic activity recorded in the tibialis anterior and gastrocnemius muscles. 3 and 5 mg/kg of mtep could inhibit the haloperidol- induced catalepsy [1].
References
[1] ossowska k,konieczny j,wolfarth s,pilc a. mtep, a new selective antagonist of the metabotropic glutamate receptor subtype 5 (mglur5), produces antiparkinsonian-like effects in rats. neuropharmacology.2005 sep;49(4):447-55.
