Peptide-based anxiolytics — Selank and the enkephalin system
Why endogenous opioid peptide modulation offers a route to anxiolysis without the sedation, dependence, or cognitive impairment of GABA-A approaches.
Conventional anxiolytic drug development has been dominated by GABA-A receptor positive modulators — the benzodiazepines and their structural relatives. These compounds are effective but carry a well-characterised burden of sedation, motor impairment, anterograde amnesia, dependence, and rebound anxiety on discontinuation.
An alternative approach is to leave the GABA-A receptor alone and instead elevate endogenous opioid peptide tone — the enkephalins and endorphins that are constitutively released and degraded throughout the CNS. By inhibiting the enzymes that degrade enkephalins (the enkephalinases), the active life of these endogenous anxiolytic peptides can be extended without administering an exogenous opioid agonist.
Selank, the prototypical peptide of this class, has been shown in published research to inhibit enkephalinase activity in a dose-dependent manner, producing measurable anxiolytic effects in animal models that compare favourably with benzodiazepines without the sedation or amnesia.
The translational data is most developed in the Russian Federation, where Selank has been studied in human anxiety populations and is approved for clinical use. Western peer-reviewed human anxiety data is sparser, and the comparative effectiveness against current first-line anxiety treatments (SSRIs and CBT) has not been comprehensively studied.