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 microg, 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 microg, 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 microg, 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.