Antidepressant activity of NEURAPAS® balance – multitarget mechanism

NEURAPAS® balance is a herbal drug combination product containing as active ingredients dry extracts of St. John's Wort (60mg), Passion flower (32mg), and Valerian root (28mg). The product has a successful history – it is more than 40 years in the German market. NEURAPAS® balance is used to relieve slightly low mood and mild anxiety as well as sleep disturbances due to symptoms of mild anxiety. However, despite numerous attempts, the mechanism of action is still discussed controversially. Only recently a comprehensive preclinical testing of NEURAPAS® balance demonstrated synergistic effects with respect to serotonin reuptake [1].

Because of the high comorbidity of anxiety, depressive and sleep disorders [2, 3], additional testing on potentially antidepressant effects of NEURAPAS® balance was performed. The transporters for noradrenaline and serotonin are key targets for antidepressant drugs. Both noradrenaline-selective and serotonin-selective reuptake inhibitors are effective against major depression and other psychiatric illnesses [4]. The inhibition of dopamine transporters is important because a dysfunction of dopaminergic mechanisms of reward is incriminated in anhedonia. Moreover, suppression of dopamine reuptake enhances sexual function and may improve cognition. The clinical finding that depressive disorders are often associated with desynchronization of internal rhythms has encouraged the idea that resetting normal circadian rhythms may have antidepressant potential. Agomelatine, a naphthalene analog of melatonin, is both an agonist of human cloned melatonergic MT₁ and MT₂ receptors and a serotonin 5-HT_2C receptor antagonist [5].

Therefore, we investigated the effects of NEURAPAS® balance in vitro. NEURAPAS® balance inhibited the uptake of [³H]-noradrenaline, [³H]-dopamine and [³H]-serotonin into rat cortical synaptosomes in a dose-dependent manner. EC₅₀ values for the inhibition of noradrenaline, dopamine and serotonin uptake were 88.6µg/ml, 90.4µg/ml and 173.9µg/ml respectively.

NEURAPAS® balance inhibited the binding of [³H]-melatonin to human recombinant MT₁ receptors in a dose-dependent manner. The EC₅₀ value was 45.9µg/ml. In addition, NEURAPAS® balance inhibited the binding of [³H]-mesulergine to recombinant human 5-HT_2C receptors in a dose-dependent manner with an EC₅₀ of 58.1µg/ml.

References: [1] McGregor GP et al. Pharmacological studies of a combination of St John's Wort, Passion Flower and Baldrian provide evidence of synergistic effects [Poster]. Phytopharmaka und Phytotherapie 2005– Forschung und Praxis, Berlin 06.-08.10.2005

[2] Müller D et al. Phytomedicine 2003; 10 (Suppl. 4): 25–30

[3] Neckelmann D et al. Sleep 2007; 30: 873–880

[4] Humble M. Acta Psychiatr Scand Suppl. 2000; 402: 28–36

[5] Millan MJ. Neurotherapeutics 2009; 6: 53–77