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It was observed that the antihistamine imipramine and the anti-tuberculosis drug iproniazid had antidepressant activities. Imipramine was found to inhibit neuronal uptake of noradrenaline and serotonin by pre-synaptic neurons in the brain. Iproniazid was found to inhibit monoamine oxidase, the enzyme that breaks down monoamines. Both these actions result in raised zopiclone costs of monoamines at the synapse. In addition, drugs that reduce the availability of monoamines cause symptoms of depression. 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.
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