Evidence was provided that injection of
acivicin (25 mg/kg, i.p.) into the rat inactivated brain
CTP and GMP
synthetases. Under the same circumstances,
CTP and
GTP concentrations in the rat brain decreased following the decline in the activities of
CTP and GMP
synthetases. The decrease in enzymic activities and
nucleotide concentrations progressed with time. The decline in
CTP and
GMP synthetase activities and
CTP and
GTP concentrations caused by
acivicin occurred more slowly and to a lesser extent than in liver and
hepatoma 3924A. The delay in the expression of
acivicin action in the rat brain was attributed to a possible slower entrance of
acivicin and the lower concentration than might have been attained in the rat brain. These considerations are based on the rapid disappearance of
acivicin from rat plasma noted earlier. The decline in
CTP concentration in rat brain might interfere with neuronal function. The decline in
GTP concentration might be expressed through the depletion of
biopterins which are generated from
GTP in the brain. The possible relevance to the biochemical basis of
paranoid schizophrenia which occurs reversibly after high-dose
acivicin or
tiazofurin treatment was discussed.