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We investigated the structure-activity relationship for the neurotrophic activity of spermine by comparing the effects of several synthetic spermine analogues on the survival of cultured rat hippocampal neurons. N,N'-bis(3-aminopropyl)-1,6-hexanediamine and N,N'-bis(3-aminopropyl)-1,3-propanediamine did not promote the neuronal survival, suggesting that the central butanediamine structure is essential for the neurotrophic activity. Furthermore, N1,N12-bis(ethyl)spermine significantly promoted the neuron survival, but its maximum effect was smaller than that of spermine, indicating that two terminal primary amines are required for full agonist activity. The structural requirement for the neurotrophic activity of spermine was different from those for any other reported activities of polyamines.
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