Slow onset of CNS drugs: can changes in protein concentration account for the delay?

A 'protein regulation hypothesis' might explain the delay in reaching a max imal clinical effect, exhibited by some antipsychotic and addicting drugs. It also suggests that crucial 'effector' proteins that mediate the actions of these drugs might have half-lives of days to weeks. In this article, the rate of onset of some antipsychotic and addicting drugs will be examined a nd a model will be used to test if a change in the concentration of a given protein(s) could cause the drug-induced effects. This hypothesis uses a mo del where protein concentrations are determined by a zero-order synthesis r ate and a first-order degradation rate. The model in its simplest form prod uces an exponential increase (or decrease) in protein concentrations over t ime, but reasonable extensions of the model can account for more complex me chanisms that allow for delayed time-courses and contributions of multiple proteins to the clinical effect.