A Control-theoretic Approach to Neural Pharmacology: Optimizing Drug Selection and Dosing. Kumar, G., Kim, S., A., & Ching, S.
A Control-theoretic Approach to Neural Pharmacology: Optimizing Drug Selection and Dosing [pdf]Paper  abstract   bibtex   
The induction of particular brain dynamics via neural phar-macology involves the selection of particular agonists from amongst a class of candidate drugs, and the dosing of the se-lected drugs according to a temporal schedule. Such a prob-lem is made nontrivial due to the array of synergistic drugs available to practitioners whose use, in some cases, may risk the creation of dose-dependent effects that significantly devi-ate from the desired outcome. Here, we develop an expanded pharmacodynamic modeling paradigm and show how it can facilitate optimal construction of pharmacologic regimens, i.e., drug selection and dose schedules. The key feature of the design method is the explicit dynamical-systems based modeling of how a drug binds to its molecular targets. In this framework, a particular combination of drugs creates a time-varying trajectory in a multi-dimensional molecular/receptor target space, subsets of which correspond to different be-havioral phenotypes. By embedding this model in optimal control theory, we show how qualitatively different dosing strategies can be synthesized depending on the particular ob-jective function considered.

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