Background
Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a synthetic heptapeptide analog of tuftsin developed at the Institute of Molecular Genetics, Russian Academy of Sciences. Its anxiolytic activity was characterized in animal models in the 1990s, and this clinical trial represented one of the first controlled evaluations of Selank in human anxiety disorder patients.
The comparison to phenazepam — a high-potency Russian benzodiazepine widely used in Eastern Europe — was clinically meaningful, as benzodiazepines remain the standard anxiolytic reference drug despite their well-known liability for dependence, cognitive impairment, and withdrawal.
Methods
62 patients with DSM-IV generalized anxiety disorder (GAD) randomized to:
- Selank 0.15 mg intranasal, twice daily for 4 weeks
- Phenazepam (benzodiazepine reference) at therapeutic dose for 4 weeks
Assessed at baseline, week 2, and week 4:
- Hamilton Anxiety Scale (HAM-A) — primary outcome
- Clinical Global Impression (CGI)
- Side effect and tolerability assessment
- Cognitive function (attention, memory tests)
Key Findings
Efficacy:
- HAM-A reduction at 4 weeks: Selank −9.8 points vs. Phenazepam −10.1 points (non-inferior, p > 0.05 for difference)
- Responder rate (≥50% HAM-A reduction): Selank 63% vs. Phenazepam 65%
- CGI improvement ratings similar between groups
Tolerability:
| Adverse Effect | Selank | Phenazepam |
|---|---|---|
| Sedation/drowsiness | Rare | Common |
| Cognitive impairment | None detected | Significant |
| Dependence/withdrawal | None | Clinically significant |
| Memory complaints | None | 40% reported |
- Selank cognitive function tests showed no impairment — cognitive scores were preserved
- Phenazepam group demonstrated significant impairment on attention and short-term memory tasks
- No withdrawal symptoms observed with Selank discontinuation
Clinical Significance
This study positioned Selank as a potentially superior anxiolytic to benzodiazepines in terms of the risk-benefit ratio:
- Equal efficacy, superior safety: Matching phenazepam’s HAM-A improvement with zero cognitive impairment and no withdrawal risk
- Intranasal delivery: Avoids hepatic first-pass metabolism; rapid onset consistent with patient preference for on-demand use
- Mechanism distinction: Selank modulates GABA-A receptors differently from benzodiazepines (partial allosteric modulation vs. full positive allosteric modulation) — which may explain the absence of dependence liability
Limitations
- Single-center Russian study; limited to Russian/Eastern European patient population
- Phenazepam comparator is less standard than lorazepam or alprazolam in international clinical practice
- No placebo arm — the study cannot establish absolute efficacy vs. no treatment
- 4-week follow-up; long-term efficacy and durability of response not assessed
- Study not published in a major English-language peer-reviewed journal; methodology details are incompletely available