(a) Risperidone, (b) 9-hydroxy risperidone, and (c) total active moiety brain concentrations (n=6 8 per group).
Repeated THC exposure reduced whole brain concentrations of risperidone, its active metabolite 9-hydroxy risperidone, and total active moiety.
There was clearly a dose-dependent effect of risperidone challenge on the brain concentrations of risperidone, 9-hydroxy risperidone, and total active moiety, but there were no significant interactions between THC and risperidone dose on the brain concentrations in the two-way ANOVA.
There was a significant effect of risperidone dose on the brain concentrations of risperidone (F 1, 26)=23.2, P<0.0001), 9-hydroxy risperidone (F 1, 26)=18.6, P<0.0001), and total active moiety (F 1, 26)=29.3, P<0.0001), but there were no significant interactions between THC and risperidone dose on these brain concentrations.
The functional free intrasynaptic concentration of the drugs is determined by simulating the competition between total active moiety and tracer at the postsynaptic D2R in a positron emission tomography radiotracer displacement study with clinical data of various antipsychotics.
Two-way ANOVA indicated that THC-treated mice had significantly decreased brain concentrations compared with vehicle of risperidone (F 1, 26)=10, P<0.01), 9-hydroxy risperidone (F 1, 26)=19.1, P<0.001), and the total active drug moiety (F 1, 26)=17, P<0.0001).
THC-treated mice had significantly decreased brain concentrations compared with vehicle controls of risperidone (Figure 3a), 9-hydroxy risperidone (Figure 3b), and the total active drug moiety (the combined brain concentration of risperidone and 9-hydroxy risperidone) (Figure 3c), following risperidone challenge.
As some of the drug compounds contained more than one "undesirable" moiety, the total number was 352.
One atom type must be the above mentioned "central" atom and another type must be a halogen, and the total charge of the moiety must be negative.
These cycles are called moiety-conserved cycles because they interconvert different forms of a chemical subgroup or moiety, the total concentration of which remains constant.
