Novel polyamine derivatives as neuroprotective agents.

The induction of an early increase in polyamine metabolism, termed "the polyamine response," is now recognized to have a critical role in the reaction of neurons to injury. Several studies in experimental animals have demonstrated that treatment with the naturally occurring polyamines spermine, spermidine, and putrescine can protect neurons from dying after the infliction of various types of neurotrauma, including mechanical injuries, neurotoxic insults, and ischemia. These findings led us to synthesize a series of polyamine derivatives of 1-aminoindan and 1-aminotetralin and to determine their effects in several in vitro and in vivo models of neurotrauma. Some of the novel compounds proved to be potent neuroprotective in these models, and one of them, N, N-di-(4-aminobutyl)-1-aminoindan, was superior to the others and to the natural polyamines themselves. We conclude that compounds based on the novel polyamine-based structures we synthesized have therapeutic potential as neuroprotective agents.