product name LY404039
Description: LY404039 (also known as Pomaglumetad) is a potent agonist of recombinant human mGlu2/mGlu3 receptors with Ki of 149 nM/92 nM, it shows >100-fold selectivity over ionotropic glutamate receptors, glutamate transporters, and other receptors. The inhibition of forskolin-stimulated cAMP formation has indicated that LY404039 was a nanomolar potent agonist of human mGlu2 (EC50 = 23 nM) and mGlu3 (EC50 = 48 nM) receptors.
References: J Pharmacol Exp Ther. 2007 Apr;321(1):308-17; J Pharmacol Exp Ther. 2008 Jul;326(1):209-17; Behav Brain Res. 2006 Aug 10;171(2):207-15.
235.22
Formula
C7H9NO6S
CAS No.
635318-11-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 1 mg/mL (4.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
Pomaglumetad
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19423171
| In Vitro |
In vitro activity: LY404039 exhibits low binding affinity to group III mGlu receptors including mGlu6, mGlu7 and mGlu8 with a Ki value more than 5 μM. LY404039 shows little affinity for ionotropic glutamate receptors, glutamate transporter subtypes, monoamine and other receptors. LY404039 potently inhibits forskolin-stimulated cAMP formation in cells expressing human mGlu2 and mGlu3 receptors. LY404039 suppresses electrically evoked excitatory activity in the striatum, and serotonin-induced L-glutamate release in the prefrontal cortex. LY404039 could modulate glutamatergic activity in limbic and forebrain areas relevant to psychiatric disorders and may be devoid of negative side effects associated with current antipsychotics and anxiolytics. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | LY404039 demonstrates higher plasma exposure and better oral bioavailability. LY404039 may be valuable in the treatment of neuropsychiatric disorders, including anxiety and psychosis. In wild-type animals, LY404039 significantly reverses d-amphetamine(AMP)-induced increase in ambulations, distance traveled, and reduced time spent at rest. LY404039 reverses phencyclidine (PCP)-evoked behaviors at 10 mg/kg. The antipsychotic-like effects of LY404039 on PCP and AMP-evoked behavioral activation are absent in mGlu2 and mGlu2/3 but not in mGlu3 receptor-deficient mice. In contrast, clozapine and risperidone inhibit PCP-evoked behaviors in both wild-type and mGlu2/3 receptor-deficient mice. LY404039 reduces responding on the EtOH in the pavlovian spontaneous recovery (PSR) test and reduces the expression of an alcohol deprivation effect (ADE) during relapse, but does not affect EtOH responding under maintenance conditions. LY404039 inhibits the expression of alcohol seeking and relapse behavior without altering alcohol self-administration behavior. Moreover, LY404039 attenuates amphetamine- and phencyclidine-induced hyperlocomotion. LY404039 could inhibit conditioned avoidance responding and also reduces fear-potentiated startle in rats and marble burying in mice. Importantly, LY404039 does not produce sedative effects or motor impairment in the conditioned avoidance task. LY404039 also increases dopamine and serotonin release/turnover in the prefrontal cortex. |
| Animal model | Separate mGlu2 and mGlu3 receptor knockout mice are established |
| Formulation & Dosage | Dissolved in 0.9% saline and the pH is adjusted to 6.0 with 1 M NaOH; 10 mg/kg; i.p. injection |
| References | J Pharmacol Exp Ther. 2007 Apr;321(1):308-17; J Pharmacol Exp Ther. 2008 Jul;326(1):209-17; Behav Brain Res. 2006 Aug 10;171(2):207-15. |
