Table A.9.
Response–Response and Temporality concordance table for the tool compound MPTP/MPP+
| (l): Dose | (m): Brain concentration | (n): KE1e (o): Inhibition of C I | (p): KE2e (q): Mitochondrial dysfunction | (r): KE3d (s): Impaired proteostasis | (t): KE4 (u): Degeneration of DA neurons of nigrostriatal pathway | (v): AO (w): Parkinsonian motor symptoms |
|---|---|---|---|---|---|---|
| 1 mg/kg infusion [1] | – | – | – |
+ 4 weeks [1] |
+c 4 weeks [1] |
No effect |
| 5 mg/kg infusion [1] | – | – | – |
++ 4 weeks [1] |
++b 4 weeks [1] |
+++ 4 weeks [1] |
|
20–30 mg/kg infusion [2, 1] |
47 μM [2]f 12 μM [1] |
+++ 4 h [2] |
+++ 4 h [2] |
+++ 4 weeks [1] |
+++a 1–4 weeks [2, 1] |
+++ 4 weeks [1] |
References: Fornai et al., 2005 [1]; Thomas et al., 2012 [2].
–: No data available.
a
Approx 50% loss of DA neurons in SNpc.
b
Approx 30% loss of DA neurons SN pc.
c
No loss of DA neurons in SN pc. Reduced level of striata DA.
d
For KE3, a dose response effect was observed.
e
For KE 1 and 2 the severity of the effect was normalised vs. the KE4.
f
After single dose MPTP administration, brain concentration was approx. 5.15 μM.