Investigation of the actions and antagonist activity of some polyamine analogues in vivo

1. The ability of three putative polyamine antagonists to antagonize behavioural changes induced by spermine was assessed.
2. Injection of an excitotoxic dose of spermine (100 μg, i.c.v.) in mice results in the development of a characteristic behavioural profile, which has two temporally distinct phases. The early events include clonic convulsions, and the later, more general excitation, includes tremor and culminates in the development of a fatal tonic convulsion.
3. Co-administration of arcaine (25 μg, i.c.v.) potentiated the early phase effects after spermine injection, but antagonized the development of spermine-induced tonic convulsions. A larger dose of arcaine (50 μg, i.c.v.) given alone resulted in the development of spermine-like body tremor and convulsions. It therefore appears that arcaine is not a pure polyamine antagonist in vivo, but may be a partial agonist.
4. Similarly, 1,10-diaminodecane appeared to act as a partial agonist in vivo, although it was less potent than arcaine.
5. In contrast, diethylenetriamine (DET) effectively inhibited the development of the early effects of spermine, but was ineffective against the spermine-induced CNS excitation and tonic convulsions.
6. It is concluded that none of the putative polyamine antagonists tested behaved as effective polyamine antagonists in vivo, although each produced some antagonism.