(A) Simulations of receptor activity using a standard four-parameter logistic equation for GPCR activation, and variable receptor expression (DeLean et al., 1978) was used to simulate the effects of over-expression of a DREADD with constitutive activity (red circles); high receptor reserve, minimal constitutive activity (blue circles); high receptor reserve + desensitization (green circles); low expression and no receptor reserve (purple circles); and low expression, no receptor reserve, and desensitization (orange circles).
(B and C) Potential pharmacokinetic parameters of CNO following high (B) and lower (C) doses. The dotted red line indicates the threshold concentration required for activation of the DREADD in situ.