product name VU 0364770
Description: VU 0364770 is a positive allosteric modulator (PAM) of mGlu4 with EC50 of 1.1 μM, it exhibits insignificant activity at 68 other receptors, including other mGlu subtypes. VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinsons disease. VU0364770 exhibits a potency of 290 ± 80 nM at rat mGlu4 and induces an 18.1 ± 1.7-fold left shift of the glutamate concentration-response curve.
References: J Pharmacol Exp Ther. 2012 Feb;340(2):404-21.
232.67
Formula
C12H9ClN2O
CAS No.
61350-00-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 47 mg/mL (202.0 mM)
Water: <1 mg/mL
Ethanol: 47 mg/mL (202.0 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19423539
| In Vitro |
In vitro activity: VU0364770 is a potent and effective positive allosteric modulator of mGlu4. VU0346770 exhibits a potency of 1.1 ± 0.2 μM at human mGlu4 in the presence of an EC20 concentration of glutamate and shifts the glutamate concentration-response curve 31.4 ± 4.0-fold to the left. VU0364770 exhibits a potency of 290 ± 80 nM at rat mGlu4 and induces an 18.1 ± 1.7-fold left shift of the glutamate concentration-response curve. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | VU0364770 shows efficacy alone or when administered in combination with l-DOPA or an adenosine 2A (A2A) receptor antagonist preladenant currently in clinical development. When administered alone, VU0364770 exhibits efficacy in reversing haloperidol-induced catalepsy, forelimb asymmetry-induced by unilateral 6-hydroxydopamine (6-OHDA) lesions of the median forebrain bundle, and attentional deficits induced by bilateral 6-OHDA nigrostriatal lesions in rats. In addition, VU0364770 enhances the efficacy of preladenant to reverse haloperidol-induced catalepsy when given in combination. The effects of VU0364770 to reverse forelimb asymmetry are also potentiated when the compound is coadministered with an inactive dose of l-DOPA, suggesting that mGlu4 positive allosteric modulator may provide l-DOPA-sparing activity. |
| Animal model | Haloperidol-Induced Catalepsy |
| Formulation & Dosage | Suspended in an aqueous solution of 10% Tween 80; 1 to 2 ml/kg i.p./s.c. or 10 ml/kg p.o.; s.c. or p.o. administration |
| References | J Pharmacol Exp Ther. 2012 Feb;340(2):404-21. |
