In conclusion, considering the practical aspects of the drug discovery process, several scenarios can be considered. For scenario I, when complete data regarding in vivo brain and plasma concentration-time profiles are available (this situation rarely occurs in the early drug discovery stage, however), the proposed hybrid model would be used for simulations at various doses and schedules theoretically. For scenario II, when only full plasma concentration-time profiles are available, compound brain concentration-time profiles can be predicted with moderate accuracy as long as brain profiles are in equilibrium with the plasma. For scenario III, when full data only for plasma and limited (at 1 h) brain concentration-time profiles are available, the proposed hybrid model can be used to accurately predict concentrations in the brain at other time points, even for profiles exhibiting non-equilibrium between the brain and plasma. We believe the proposed model structure would be useful for researchers engaged in the challenge of discovering new CNS drugs. On the other hand, we only examined a total of 103 in-house compounds and most of them were structurally different from FDA-approved compounds.