Selank

In a randomised comparative trial in 62 adults with generalised anxiety disorder or neurasthenia — 30 given Selank, 32 given the benzodiazepine medazepam — anxiolytic effects on the Hamilton, Zung and CGI scales were similar between arms, and only the Selank arm additionally showed antiasthenic and psychostimulant effects. Patients had a shortened serum leu-enkephalin half-life at baseline that correlated with illness duration and with the severity of anxiety, asthenia and autonomic symptoms; this parameter rose, with stronger positive correlations with anxiety level, during Selank treatment and chiefly in the generalised anxiety subgroup.³

In a randomised trial in 70 adults with anxiety-phobic, hypochondriacal and somatoform disorders, adding Selank to phenazepam (40 patients) rather than giving phenazepam alone (30 patients) brought the HDRS response forward in time and reduced UKU-rated side effects of the benzodiazepine — sedation, asthenia, attention and memory impairment, lengthened sleep, sexual disturbance, emotional indifference and orthostatism — both during co-administration and after the tranquilliser was withdrawn.⁴

In a placebo-controlled resting-state fMRI study of 52 healthy adults scanned before and 5 and 20 minutes after a single injection of Selank, Semax or placebo, functional connectivity between the right amygdala and a right-hemisphere fusiform, temporal and parahippocampal region differed both between groups and between scan conditions.¹⁵

In human blood plasma in vitro, Selank inhibited enzymatic hydrolysis of enkephalin dose-dependently with an IC50 of 15 uM, more potently than the peptidase inhibitors bacitracin and puromycin; in the same report, patients with generalised anxiety disorder — but not those with panic disorder or agoraphobia — showed shortened plasma enkephalin half-life and reduced total enkephalinase activity.⁷

In outbred rats made morphine-dependent and precipitated into withdrawal with naloxone, a single intraperitoneal injection of Selank in the 0.3 mg/kg arm reduced the total withdrawal index by 39.6% and raised the tactile sensitivity threshold 9-fold relative to active control, against 49.3% and 13-fold in the diazepam 2 mg/kg arm; convulsive reactions, ptosis and posture disorders were attenuated at p<0.0001.¹⁶

In outbred rats given 10% ethanol as their only fluid for 30 weeks, Selank in the 0.3 mg/kg arm over 7 days prevented the memory and attention disturbances that emerged during alcohol withdrawal in the object recognition test (p<0.01) and blocked the ethanol-induced rise in BDNF content in the hippocampus and frontal cortex (p<0.05).¹⁷

In BALB/c and C57BL/6 mice dosed for 5 days, Selank produced anxiolytic and nootropic effects on the elevated plus maze only in the high-anxiety BALB/c strain, and the receptor changes tracked the route: the intraperitoneal arm raised frontal-cortex GABA-receptor binding sites by 38% with no change in hippocampal NMDA binding, whereas the intranasal arm raised NMDA binding-site density by 23% with no change at GABA receptors.¹³

In rat hippocampal slices, bath-applied Selank increased both the amplitude and the discharge rate of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons — in some cells after a transient decrease — and showed no significant dose-dependence across the 1-8 uM range tested.¹²

In rat frontal cortex sampled 1 and 3 hours after a single 300 ug/kg dose of Selank or of GABA itself, 45 of 84 neurotransmission-related genes had altered expression at 1 hour and 22 at 3 hours, and the 1-hour changes produced by Selank correlated positively with those produced by GABA.¹⁰

In mice, intraperitoneal Selank across the 0.01, 0.1, 1.0 and 10.0 mg/kg arms reduced apomorphine-induced verticalisation comparably to olanzapine at 0.1 and 1.0 mg/kg, and the effect was abolished by naloxone 10 mg/kg; in parallel radioreceptor assays on rat brain membranes Selank displaced neither 3H-spiperone from D2 dopamine sites (EC50 > 100 uM) nor 3H-DADLE from delta/mu-opioid sites (EC50 > 40 uM).⁹

In outbred white rats subjected to 20 days of sensory-contact social confrontation, which raised serum IL-1beta, IL-6 and TGF-beta1 significantly above intact controls — the rise in TNF-alpha and the fall in IL-4 under stress were non-significant trends — daily intraperitoneal Selank in the 100 ug/kg arm lowered IL-1beta, IL-6, TNF-alpha and TGF-beta1 to approximately control values.¹⁸

Against influenza A/Aichi 2/68 (H3N2), Selank added to cell culture 24 hours before inoculation completely suppressed viral reproduction, and in infected laboratory mice survival was highest under the same pre-exposure schedule; in vivo the peptide induced interferon-alpha gene expression without altering IL-4, IL-10 or TNF-alpha.¹⁹