I. The development of amine substituted analogues of MPTP as unique tools for the study of MPTP toxicity and Parkinson's disease

Abstract

We are currently developing amino-substituted MPTP analogues as useful probes for understanding the mechanism of MPTP toxicity and Parkinson's disease. One analogue, 4′-amino MPTP, induces a loss of striatal dopamine and is thus a suitable substitute for MPTP. This probe will be used as a histologically fixable MPTP which can be used to answer detailed anatomical questions concerning the sites of MPTP, MPP + uptake and storage. In addition, antibodies have been raised against MPTP and MPP + in rabbits using diazo-linked bovine serum albumin conjugates. The antibodies have been characterized with regard to their recognition of relevant structural analogues using an enzymelinked immunoassay (ELISA) procedure. Antibodies to MPTP detected MPTP in mouse brain extracts derived from as little as 5 μg of tissue. The antibodies will be used for immunohistochemical localization of 4′-NH 2-MPTP and 4′-NH 2-MPP + in brain, as well as probes for the screening of parkinsonian brain tissue for any MPTP- or MPP +-like materials which might exist.