79 early PD vs 32 HV cohort tail (cleaner copy at 20240722_182938), Dopamine Receptor Imaging continued (Booth 2015 #1745 raclopride PET / Bezard 2001 #1748 MPSP Monkey ABL plots), Druggability section opener (Lipophilicity definition / CNS penetration formulas / Kpuu values for paracetamol / HDACA / MOC950 / NLRP3 inhibitor / NoeITherm / AC immune compounds / selinexor; Rat Brain/Plasma Ratio bar chart)
Dopamine Receptor Imaging (continued)
(Bezard, 2001 #1748) MPSP Monkey ABL
Figure 4. Examples of D1 (A) and D2 (B) binding autoradiography studies at the carbamoyl level of the striatum.
The horizontal bar marks for each comparison indicate the mean percentage of D2-R binding. Symptomatic Parkinsonism in monkeys can be detected as a decrease of D2 receptor binding in the striatum compared with control animals after 5 weeks of MPTP-treatment, B): (16) (Mp), the Pre-S, P, but the Pre-PD, indicates the mid-stage of monkeys, while the late-stage of monkeys are referred to as ‘sym1’ or ‘sym2’, the appearance of bradykinesia and motor impairment is noted to be dose, the Pre-PD MPTP, an explosion of motor symptoms (E.g. fight); (the binding rate from the moonsphere) is correlated to symptomatology, due to the low binding rate, the meaningful loss of D2 binding represents the most striking transition.
js: not informative tool, as shown above, not correlated at all with nigral neuronal loss
Druggability
| Lipophilicity | (Agroni et al. 2020, PMID): molecular weight of 200 and lipophilicity of - ~ 2 - logD7.4 ~ 5, and a triangle apex molecular weight of 450 and logD7.4 ~ 1.0 - 2.0. | ||||||||||||||||||||||||
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| CNS penetration |
fu,b: unbound fraction in brain Total Brain/Plasma Ratio (그래서 이건 단위가 없구나..도. 표현된치 같음) Kp = AUCbrain/AUCplasma brain · 의 비 비/total brain blood Below (Sammerfield, 2016 #1987) Kp,uu values were derived from steady-state intravenous CNS penetration studies in rodents. Example - paracetamol Kp,uu ~ 1 | ||||||||||||||||||||||||
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