PRELIMINARY INVESTIGATIONS OF SOME DERIVATIVES OF OXAMNIQUINE

Oxamniquine is a potent schistosomicide used clinically in the treatme nt of infections due to Schistosoma mansoni. Although relatively well tolerated, some central nervous system (CNS) effects characterised by convulsions have been reported in a small proportion of the population receiving this drug. Oxamniquine, the major metabolite and the second ary alcohol have been screened for convulsant activity by assessing th eir ability to potentiate catechol induced seizures in urethane anaest hetised mice. Significant (p<0.05) potentiation was observed with subc onvulsive doses (1.5 mg/kg) of strychnine. In contrast, oxamniquine an d the secondary alcohol, each at 200 mg/kg ip, bath produced significa nt (p<0.05) depressions of seizures in this model whereas Ilo effect w as seen following 140 mg/kg ip of the acid derivative. These results i ndicate anticonvulsant rather than convulsant activity in oxamniquine and the alcohol derivative. The failure to observe any effect with the acid derivative may have been due to poorer CNS penetration.