INVESTIGATION OF THE ACTIONS AND ANTAGONIST ACTIVITY OF SOME POLYAMINE ANALOGS IN-VIVO

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