Kitaichi Y, Inoue T, Nakagawa S, Boku S, Koyama T. Effects of combined treatment with clorgyline and selegiline on extracellular noradrenaline and serotonin levels.

Objective Combined treatment with clorgyline, an irreversible monoamine oxidase (MAO)-A inhibitor, and selegiline, an irreversible MAO-B inhibitor, reportedly increases extracellular serotonin levels in the raphe nuclei more than clorgyline does alone. However, the effects of combination of these MAO inhibitors on extracellular noradrenaline have not been reported.

Methods Using in vivo microdialysis, we measured extracellular noradrenaline and serotonin levels after administration of clorgyline and/or selegiline in the medial prefrontal cortex of rats.

Results Administration of clorgyline (10 mg/kg) significantly increased both extracellular serotonin and noradrenaline levels. Combined treatment using clorgyline (10 mg/kg) and selegiline (3 mg/kg) increased extracellular serotonin and noradrenaline levels more than each drug alone did.

Conclusions These findings of this study suggest the augmented antidepressant action of the combination of MAO-A inhibition and MAO-B inhibition. The addition of a MAO-A inhibitor to selegiline or increasing dose of selegiline to achieve full MAO-A inhibition might be the promising strategy for the antidepressant treatment in partial responders or non-responders to selegiline.

A healthy, balanced diet is essential for both physical and mental well-being. Such a diet must include an adequate intake of micronutrients, essential fatty acids, amino acids and antioxidants. The monoamine neurotransmitters, serotonin, dopamine and noradrenaline, are derived from dietary amino acids and are involved in the modulation of mood, anxiety, cognition, sleep regulation and appetite. The capacity of nutritional interventions to elevate brain monoamine concentrations and, as a consequence, with the potential for mood enhancement, has not been extensively evaluated. The present study investigated an extract from oregano leaves, with a specified range of active constituents, identified via an unbiased, high-throughput screening programme. The oregano extract was demonstrated to inhibit the reuptake and degradation of the monoamine neurotransmitters in a dose-dependent manner, and microdialysis experiments in rats revealed an elevation of extracellular serotonin levels in the brain. Furthermore, following administration of oregano extract, behavioural responses were observed in mice that parallel the beneficial effects exhibited by monoamine-enhancing compounds when used in human subjects. In conclusion, these data show that an extract prepared from leaves of oregano, a major constituent of the Mediterranean diet, is brain-active, with moderate triple reuptake inhibitory activity, and exhibits positive behavioural effects in animal models. We postulate that such an extract may be effective in enhancing mental well-being in humans.