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From such observations the monoamine theory of depression and mania was formed: Depression is due to an absolute or relative decrease in monoamines, or a decrease in receptor sensitivity, at certain receptor sites in the brain. Mania is due to an absolute or relative excess of monoamines or an increase in receptor sensitivity at these sites. Even after years of research, it is still not clear which receptor sites or which monoamines are involved, although noradrenaline, serotonin and dopamine are all implicated. Neither does the theory explain how mania and depression can exist in the same patient. Much research has involved investigation of cerebrospinal fluid, blood and urine of patients to see if there are any abnormalities of monoamine metabolites.

Adverse effects of fluorouracil are less likely, but similar to methotrexate. Cytarabine is a pyrimidine analogue, which is incorporated into both RNA and DNA and interferes with the action of DNA polymerase. Cytarabine is used to treat leukaemia. Adverse effects of cytarabine are bone marrow suppression and gastrointestinal disturbances. Some cytotoxic antibiotics prevent cell division by direct action on DNA. Others form polynucleotides, which inhibit transcription of DNA to RNA and therefore suppress protein synthesis.

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