У кого нибудь есть цифры по части аффинитета бупра к белкам насосам и рецепторам?
Особенно интересует сродство к никотиновым рецепторам (в цифрах)...
https://en.wikipedia.../wiki/Bupropion
The binding affinity (Ki) and inhibitory potency (i.e., the half maximal inhibitory concentration or IC50) of bupropion at the human dopamine transporter are 526 nanomolar (nM) and 443 nM, respectively
Ki
NET 526
DAT 443
https://www.scienced...ydroxybupropion
Bupropion yields two active metabolites (including hydroxybupropion) that may accumulate and contribute to antidepressant activity by blocking NET. Peak action is seen in 3 hours, with a half-life of approximately 20 hours. Bupropion is metabolized by CYP2B6, which may cause the drug to have an important drug interaction profile. Smoking does not alter its kinetics. Nearly 80% of an orally administered dose is excreted as inactive metabolites in the urine.
метаболиты почти не трогают насос дофамина, только норадреалина
если пить с флуоксетином по идее неметаболизированного будет больше, и больше будет работать по дофамину. но у него меньше t1/2 относительно метаболитов.
метаболит Hydroxy bupropion
IC50
NET 1.7 µM
DAT >10 µM
Hydroxy bupropion is a mixture of enantiomers produced by the metabolism of buproprion by cytochrome P450 2B6.1,2 Compared with buproprion, this racemic mixture produces equal inhibition of norepinephrine reuptake (IC50 = 1.7 µM) and much weaker inhibition of dopamine reuptake (IC50 >10 µM).3 Moreover, hydroxyl bupropion isomers are potent antagonists of nicotinic receptors, suggesting that
they may substitute for bupropion in smoking cessation.3,4,2
FIGURE 12.12. Electrospray ionization mass spectra of bupropion (solid line) and [2H6]hydroxybupropion (dotted line). Note that the protonated molecular ions (MH+, respectively, at m/z 256 and 262) exhibit characteristic chlorine isotope peaks that have 25% of the molecular ion intensity at m/z 258 and 264, due to the relative natural abundance of 35Cl and 37Cl. This is reflected also in the MH+–H2O ions at m/z 238 and 244. Data provided by R.L. Walsky and R.S. Obach, Pfizer, New York, NY.
равновесная концентрация 5-8 дней
Bupropion and its metabolites exhibit linear kinetics following single doses and chronic administration of bupropion dose strengths of 150–450 mg/d [44,48,49]. Following daily dosing, bupropion and its metabolites generally reach steady state in 5–8 d
Tmax
The approximate Tmax value for bupropion is 1.5–5 h depending on the drug-product formulation (IR, SR, and XL, respectively), for hydroxybupropion it is 7 h, and for threo-bupropion and erythro-bupropion it is 8 h. The Cmax values of hydroxybupropion and threo-bupropion are four- to eightfold and three- to fivefold greater, respectively, than that of bupropion [45,50].
хотя не все как-то сходится с таблицей 1 из русской википедии. https://ru.wikipedia.../wiki/Бупропион