N-Acetyl Selank Amidate

This study combined an in vitro enzymology arm with a clinical observation arm. The authors first characterised enkephalin-degrading enzyme activity in the plasma of patients with generalized anxiety disorder, panic disorder, and agoraphobia (DSM-IV criteria), reporting a shortened enkephalin half-life and reduced total enkephalinase activity in the generalized-anxiety cohort relative to controls. The heptapeptide Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) then dose-dependently inhibited enzymatic hydrolysis of plasma enkephalin in vitro, with an IC50 of approximately 15 μM, and was more potent in this assay than the reference peptidase inhibitors bacitracin and puromycin. The authors propose that Selank's reported anxiolytic activity may be linked to its inhibition of enkephalin breakdown, allowing endogenous enkephalin signalling to persist longer in plasma.

The body naturally makes small molecules called enkephalins that help dampen stress signals. Enzymes in the blood break these enkephalins down quickly. The researchers showed that, in test-tube experiments, Selank slows those breakdown enzymes — making it more effective than two well-known reference inhibitors. They also noted that patients with generalized anxiety had unusually fast enkephalin breakdown to begin with. The proposal: Selank may help keep the body's own calming signals around for longer, rather than acting like a sedative.

Using qPCR across a panel of 84 genes involved in GABAergic neurotransmission in cultured IMR-32 neuroblastoma cells, the authors compared expression changes induced by GABA, Selank, and olanzapine. Selank alone did not significantly change the mRNA level of the GABA-related genes in this cell line, suggesting that Selank does not act as a direct transcriptional regulator of the GABAergic gene set in IMR-32 cells. The authors interpret this in the context of prior literature showing in vivo effects of Selank on GABAergic signalling, and propose that Selank's interaction with the GABAergic system in intact tissue may occur through allosteric or indirect mechanisms rather than direct gene-expression modulation in neurons.

GABA is the brain's main calming neurotransmitter. The researchers wanted to know whether Selank changes how strongly nerve cells turn on the genes that handle GABA signalling. In a human neuron-like cell line, Selank by itself did not change those gene levels in a measurable way. The authors suggest Selank probably influences the GABA system indirectly — perhaps by changing how existing receptors respond to GABA — rather than by reprogramming the cell's gene activity.