The factors that co-determine the amount of drug that enters and is maintained in brain following its systemic administration were analyzed to aide in the safer use of drugs in the elderly and the development of central nervous system therapeutics. Rationale strategies were developed to design selective, long-duration and centrally active cholinesterase inhibitors for the palliative treatment of Alzheimer's disease and agents also were developed to improve the treatment of malignant brain tumors. Specifically, novel analogues of physostigmine were developed as cognitive enhancers and a novel lipophilic anticancer alkylating agent, a tertiary butyl ester of chlorambucil, was developed for brain tumor treatment. Further, therapeutics and strategies are being developed for the treatment of neurologic diseases, of drug abuse and to improve drug delivery to brain.
