Neuroimmunophilin ligands were derived from the immunosuppressant, rapamycin (FK-506), which had potent neurotrophic properties.74 The first of these NCEs, GPI-1046 71, demonstrated a 'sprouting' effect by increasing tyrosine hydroxylase immunoreactivity in the striatum of MPTP-treated mice and reduced amphetamine-induced ispilateral rotations in unilateral 6-OHDA-lesioned rats. GPI-1046 lacked efficacy in MPTP-treated nonhuman primates. A second-generation NCE, GPI-1485, was advanced to Phase II clinical trials to investigate its potential neuroprotective effects on dopaminergic neurons but was discontinued.

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