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The substitution of carboxamide at the alkyl terminal (KL2, KL4 and KL5) or removal of the nitrile group from the dihydropyridine ring (KL6) moderately reduced their adjuvant activity (Extended Data Fig

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Furthermore, the specific volume of distribution of MAO-A was elevated an average of 34% throughout the brain during major depression.22 The magnitude of this finding, together with the absence of any other compelling explanation for monoamine loss during major depressive episodes, led the investigators to conclude that elevated MAO-A was in fact the primary cause of monoamine lowering during major depression.22 Mechanism of MAO Inhibition The MAOIs were first developed in the 1950s