On March 15, 2018, Petrov, Konstantin; Zueva, Irina; Kovyazina, Irina; Sedov, Igor; Lushchekina, Sofya; Kharlamova, Alexandra; Lenina, Oksana; Koshkin, Sergei; Shtyrlin, Yurii; Nikolsky, Evgeny; Masson, Patrick published an article.Computed Properties of 626-48-2 The title of the article was C-547, a 6-methyluracil derivative with long-lasting binding and rebinding on acetylcholinesterase: Pharmacokinetic and pharmacodynamic studies. And the article contained the following:
C-547, a potent slow-binding inhibitor of acetylcholinesterase (AChE) was i.v. administered to rat (0.05 mg/kg). Pharmacokinetic profiles were determined in blood and different organs: extensor digitorum longus muscle, heart, liver, lungs and kidneys as a function of time. Pharmacokinetics (PK) was studied using non-compartmental and compartmental analyses. A 3-compartment model describes PK in blood. Most of injected C-547 binds to albumin in the bloodstream. The steady-state volume of distribution (3800 mL/kg) is 15 times larger than the distribution volume, indicating a good tissue distribution. C-547 is slowly eliminated (kel = 0.17 h-1; T1/2 = 4 h) from the bloodstream. Effect of C-547 on animal model of myasthenia gravis persists for more than 72 h, even though the drug is not anal. detectable in the blood. A PK/PD model was built to account for such a pharmacodynamical (PD) effect. Long-lasting effect results from micro-PD mechanisms: the slow-binding nature of inhibition, high affinity for AChE and long residence time on target at neuromuscular junction (NMJ). In addition, NMJ spatial constraints i.e. high concentration of AChE in a small volume, and slow diffusion rate of free C-547 out of NMJ, make possible effective rebinding of ligand. Thus, compared to other cholinesterase inhibitors used for palliative treatment of myasthenia gravis, C-547 is the most selective drug, displays a slow pharmacokinetics, and has the longest duration of action. This makes C-547 a promising drug leader for treatment of myasthenia gravis, and a template for development of other drugs against neurol. diseases and for neuroprotection. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Computed Properties of 626-48-2
The Article related to myasthenia gravis c547 pharmacodynamics pharmacokinetics acetylcholinesterase, 6-methyluracil, acetylcholinesterase, binding kinetics, myasthenia gravis, pharmacodynamics, pharmacokinetics and other aspects.Computed Properties of 626-48-2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia