| Chemical Properties | Back Directory | [Boiling point ]
608.790±65.00 °C(Press: 760.00 Torr)(predicted) | [density ]
1.481±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted) | [form ]
Solid | [pka]
5.397±0.25(predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Uses]
VU6019650 is a potent and selective orthosteric antagonist of M5 mAChR (IC50=36 nM), can be used for opioid use disorder (OUD) relief. VU6019650 can cross blood brain barrier, potentially modulates the mesolimbic dopaminergic reward circuitry. VU6019650 blocks Oxotremorine M iodide (HY-101372A) induced increases of neuronal firing rates of midbrain dopamine neurons in the ventral tegmental area (VTA)[1][2]. | [in vivo]
VU6019650 (10-56.6 mg/kg; i.p.; single dose) inhibits the rewarding effects of Oxycodone and reduces oxycodone self-administration in rats[1].
Pharmacokinetic Analysis in rats[1]
| Route | Dose (mg/kg) | t(term) (min) | MRT (min) | Cl_obs (mL/min/kg) | Vdss(L/kg) | AUC (ng·h/mL) | | i.v. | 1 | 876 | 644 | 56.5 | 36.6 | 301 | | Route | Dose (mg/kg) | Cmax (ng/mL) | Tmax (h) | AUG (ng·h/mL) | F (%) | | | p.o. | 10 | 433 | 0.25 | 830 | 27.6 | |
| Animal Model: | Oxycodone-induced rats[1] | | Dosage: | 10 mg/kg, 30 mg/kg, and 56.6 mg/kg in 10% Tween | | Administration: | Intraperitoneal injection; single dose | | Result: | Dose dependently reduced the number of reinforcers earned when Oxycodone is self-administered at a dose of 56.6 μg/kg/infusion. |
| [IC 50]
mAChR5: 36 nM (IC50) | [References]
[1] Garrison AT, et al. Development of VU6019650: A Potent, Highly Selective, and Systemically Active Orthosteric Antagonist of the M5 Muscarinic Acetylcholine Receptor for the Treatment of Opioid Use Disorder. J Med Chem. 2022 Apr 28;65(8):6273-6286. DOI:10.1021/acs.jmedchem.2c00192
[2] Capstick RA, et al. Discovery of a potent M5 antagonist with improved clearance profile. Part 1: Piperidine amide-based antagonists. Bioorg Med Chem Lett. 2022 Nov 15;76:128988. DOI:10.1016/j.bmcl.2022.128988 |
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