Methods to optimize CNS exposure of drug candidates

Among the most devastating disorders of our time, neurologic and psychiatric diseases combine to cause more disability than any other disease area. One of the key objectives within the medicinal chemistry discipline is to design molecules that penetrate into the target tissue. The objective of tissue specificity can be to gain or restrict drug access to the compartment of interest. This article briefly reviews the progress of CNS drug discovery over the past few decades. Included are the most recent efforts to harness structural and physicochemical properties assessment coupled with the impact of efflux transporters in determining brain penetration and the translation from rodent to human brain tissue targeting.