Wistar rats were injected with the
carcinogen 3-MC. The effect of
psychoactive drugs on
tumor-bearing rats was examined with respect to
tumor growth, survival time, and remissions. CNS drugs were given both prophylactically and therapeutically.
Psychopharmaceuticals like
piracetam and
pyrithioxin as well as
catecholamine-agonists like
imipramine had a definite
antineoplastic effect. This effect was increased when combined with other CNS drugs and, in particular, the combination of
piracetam with chemotherapeutic agents resulted in a high rate of remission and reduced the toxicity of
chemotherapy. Surgical removal of
tumors and subsequent treatment with CNS drugs led to a high rate of cure without
metastasis. After
tumor appearance, we found cerebral neuropathological changes as described in the
paraneoplastic syndrome. The EEGs of 3-MC-injected rats showed early pathognomic changes in frequency and amplitude. Similar changes were found in animals with
transplantation tumors (Walker
carcinoma and
Jensen sarcoma). The EEG pattern was normalized after surgical removal of
Jensen sarcoma and treatment with
piracetam and
pyrithioxin. These EEG changes might have occurred as a result of transmitter metabolism; ie,
carcinogenesis of both induced
tumors and transplanted
tumors was accompanied by an increase of
GABA content in hypothalamus and hippocampus and a reduced concentration of monoamines or their metabolites in hypothalamus and caudate nucleus. Long-term treatment with
piracetam or
imipramine again arrested all these changes. More recently, we achieved good results with the combination of CNS drugs and cAMP agonists. We therefore conclude that
carcinogenesis interferes with the metabolism or availability of
cyclic nucleotides and transmitters that regulate their level. CNS drugs may effect a new balance resulting in
tumor suppression.