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Blier, P. et al.

Blier, Gobbi, Haddjeri, Santarelli, Mathew, Hen,

Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response.

Substance P (neurokinin-1 [ NK1]) receptor antagonists appear to be effective antidepressant and anxiolytic agents, as indicated in 3 double-blind clinical trials. In laboratory animals, they promptly attenuate the responsiveness of serotonin (5-hydroxytryptamine [5-HT]) and norepinephrine (NE) neurons to agonists of their cell-body autoreceptors, as is the case for some antidepressant drugs that are currently in clinical use. Long-term, but not subacute, antagonism of NK1 receptors in rats increases 5-HT transmission in the hippocampus, a property common to all antidepressant treatments tested thus far. This enhancement seems to be mediated by a time-dependent increase in the firing rate of 5-HT neurons. Mice with the NK1 receptor deleted from their genetic code also have an increased firing rate of 5-HT neurons. Taken together, these observations strongly suggest that NK1 antagonists could become a new class of antidepressant and anxiolytic agents.[1]

References

Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response. Blier, P., Gobbi, G., Haddjeri, N., Santarelli, L., Mathew, G., Hen, R. Journal of psychiatry & neuroscience : JPN. (2004) [Pubmed]

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