Preliminary investigations of some derivatives of oxamniquine.
Oxamniquine is a potent schistosomicide used clinically in the treatment 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 secondary alcohol have been screened for convulsant activity by assessing their ability to potentiate catechol induced seizures in urethane anaesthetised mice. Significant (p < 0.05) potentiation was observed with subconvulsive doses (1.5 mg/kg) of strychnine. In contrast, oxamniquine and the secondary alcohol, each at 200 mg/kg ip, both produced significant (p < 0.05) depressions of seizures in this model whereas no effect was seen following 140 mg/kg ip of the acid derivative. These results indicate 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.
Karekezi
C W
CW
Department of Chemistry, University of Technology, Loughborough, Leicestershire, UK.
Lucas
P D
PD
Marples
B A
BA
Salt
W G
WG
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D051379:Mice; D010073:Oxamniquine / Q000031:analogs & derivatives* / Q000633:toxicity; D012556:Schistosomicides / Q000494:pharmacology* / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced
D000927:Anticonvulsants; D012556:Schistosomicides; D010073:Oxamniquine