Selank: Side Effects

Safety Notice#

The safety profile of Selank in humans has not been established through controlled clinical trials. The information below is derived primarily from animal studies and should be interpreted accordingly.

Documented Adverse Effects#

Animal studies

• Rats, repeated dosing 4 weeks (IP 0.3 mg/kg daily): No mortality or organ pathology reported; authors note no inhibitory side effects even at high doses. Body weight increased in all groups; TP‑7 group gained weight more slowly than passive controls, attributed largely to injection procedure; overall, no peptide‑attributable toxic effects were described (n=8 per group). Severity: none to mild (relative weight gain difference); frequency: not quantified beyond group means.
• Rats, 2‑week intranasal course 300 μg/kg (± diazepam) with behavioral testing: Across treated groups, anxiety‑like and exploratory metrics deteriorated over the 2‑week course (e.g., large reductions in open‑arm time), with Selank alone showing less pronounced deterioration than some comparators; no systemic toxicity, mortality, or organ pathology were reported. Severity: behavioral changes only; frequency: quantified as group‑level behavioral metrics, not adverse‑event incidence. Tolerance to Selank was not observed over 14 days (n=48 total).
• Review‑level preclinical claims: Tuftsin showed no apparent toxicity in vivo; in nonhuman primates (young and elderly monkeys) Selank was reported to have prolonged effects “with no side effects” in cited studies; anticoagulant/antiplatelet properties were noted alongside a claim of no bleeding complications even in overdose. These are qualitative review statements without tabulated frequencies.

Human reports

• Russian comparative clinical data with UKU monitoring (anxiety/neurasthenic disorders): Typical benzodiazepine adverse effects observed with phenazepam (sedation, asthenia, emotional indifference, sexual dysfunction, orthostatism). When Selank was co‑administered with phenazepam (nasal 0.15% formulation in clinical practice), several adverse‑event items were significantly reduced in frequency and/or severity compared with phenazepam alone (p<0.05 to p<0.001) over 7–21 days; tables suggest lower proportions for multiple AE items in the combination arm, but precise AE‑by‑AE percentages are not cleanly extractable from the presented figures. Severity: reductions in sedation, cognitive slowing, and orthostatic complaints; no serious systemic toxicity described. Sample sizes: illustrative tables show approximately n≈30 (phenazepam) vs n≈40 (combination), with a subset continuing Selank to day 21 (медведев2015оптимизациятерапиитревожных pages 3-5, медведев2015оптимизациятерапиитревожных pages 5-6, медведев2015оптимизациятерапиитревожных pages 6-7).
• Review in a clinical pharmacology journal: Harmful effects and abuse potential of Selank are poorly characterized; human trials have been small and short, and long‑term side effects remain unestablished. This underscores the scarcity of robust frequency/severity data in humans outside regional reports (doyno2021sedative‐hypnoticagentsthat pages 10-12, doyno2021sedative‐hypnoticagentsthat pages 9-10).

Interpretation

• Animals: Across reported doses and durations, no mortality or organ pathology has been documented in the cited rat studies; adverse observations consist mainly of behavioral changes under prolonged testing paradigms, with one study attributing slower weight gain primarily to injection rather than the peptide. Reported severity is mild and frequency is not provided as event rates.
• Humans: The best available monitored dataset suggests that, in short courses and often as an adjunct to phenazepam, Selank regimens were associated with fewer benzodiazepine‑typical adverse effects compared with benzodiazepine alone, without emergent serious toxicities in the observed interval. However, precise AE frequencies are not fully resolvable from the available tables, and external reviews emphasize that long‑term and rare adverse effects are not well characterized due to small, short trials (медведев2015оптимизациятерапиитревожных pages 3-5, медведев2015оптимизациятерапиитревожных pages 5-6, медведев2015оптимизациятерапиитревожных pages 6-7, doyno2021sedative‐hypnoticagentsthat pages 10-12).

Limitations and gaps

• Frequency/severity quantification is limited: animal studies report group behaviors rather than AE incidence; human reports provide significance testing but not consistently itemized percentages suitable for meta‑summary. Long‑term safety, abuse potential, and rare events remain insufficiently characterized (doyno2021sedative‐hypnoticagentsthat pages 10-12).

• Documented adverse effects in animals: No lethality or organ pathology; mild findings include relative slowing of weight gain under injection protocols and behavioral changes during prolonged testing; severity mild; frequency not tabulated.

• Documented adverse effects in humans: In short‑term clinical use, Selank co‑administration appears to reduce frequency/severity of several benzodiazepine‑related adverse effects (sedation, asthenia, cognitive slowing, orthostatic symptoms) compared with benzodiazepine alone; serious adverse events not described in the cited reports; precise frequencies not fully extractable; long‑term and rare adverse effects remain unknown (медведев2015оптимизациятерапиитревожных pages 3-5, медведев2015оптимизациятерапиитревожных pages 5-6, медведев2015оптимизациятерапиитревожных pages 6-7, doyno2021sedative‐hypnoticagentsthat pages 10-12).

Animal Study Safety Data#

We synthesized adverse-effect evidence on Selank (TP‑7), including animal studies and human reports, emphasizing frequency and severity where available. A structured summary is provided below.

Contraindications#

Objective: define Selank and the scope. Selank is a tuftsin-derived heptapeptide (Thr–Lys–Pro–Arg–Pro–Gly–Pro) developed as 0.15% intranasal drops in Russia for anxiolytic use. The question asks for known contraindications and drug–drug interactions, and for theoretical interactions based on mechanism (GABAergic/monoaminergic/opioidergic/immunomodulatory).

Known contraindications and labeled interactions

• Explicit labeled contraindications: Peer‑reviewed reviews and mechanistic papers do not provide labeled contraindications or formal drug–drug interaction sections for Selank. Regulatory-style package insert data were not available in the retrieved sources.
• Documented clinical drug–drug interactions: None identified in the reviewed literature.

Precautions driven by evidence gaps and route of administration

• Pregnancy and lactation: No human safety data were found; use is unsupported due to insufficient evidence.
• Pediatrics: Insufficient clinical data to establish safety/efficacy.
• Intranasal route/mucosal disease: Intranasal Selank exhibits rapid absorption into plasma (≈30 s) and brain (≈2 min) with high reported bioavailability; while no explicit warnings were listed, mucosal disease or barrier disruption could theoretically alter exposure.
• Hypersensitivity: As a peptide, general caution for allergic reactions is prudent, though explicit cases were not reported in the reviewed sources.

Theoretical drug interactions based on mechanism of action

• CNS depressants and GABAergic agents (e.g., benzodiazepines, alcohol): Selank produces anxiolysis with benzodiazepine-like spectrum and modulates GABAergic-related gene expression/inhibitory interneuron activity; additive CNS effects or modulation of response are plausible.
• Serotonergic agents (SSRIs, SNRIs, MAOIs): Selank alters serotonin levels and metabolism in brain regions; combined use could shift serotonergic tone, potentially changing efficacy or adverse-effect risk.
• Dopaminergic agents (L‑DOPA, antipsychotics, psychostimulants): Selank modulates dopamine metabolism and counteracts apomorphine‑induced hyperdopaminergic behavior, implying potential pharmacodynamic interaction with dopaminergic drugs.
• Opioid agonists/antagonists and enkephalinase‑targeted agents: Selank inhibits enkephalin‑degrading enzymes, prolonging Leu‑enkephalin half‑life, and some behavioral effects are naloxone‑sensitive; interactions with opioids or enkephalinase modulators are theoretically possible.
• Immunomodulators and vaccines: Selank modulates cytokine gene expression and interferon responses and influences Th1/Th2 balance; theoretical effects on responses to immunomodulatory drugs or vaccines should be considered.
• Anticoagulants/antiplatelets: Reports in the peptide class note anticoagulant, fibrin‑depolymerization, and antiplatelet activities, and related peptide Semax interacts with heparin and stimulates anticoagulation in models; thus an additive bleeding risk is a theoretical concern.
• Agents affecting monoamine metabolism (e.g., MAOIs, COMT inhibitors): Because Selank affects monoamine levels and metabolism, coadministration with monoamine‑metabolism inhibitors could alter neurotransmitter tone.

Formulation and pharmacokinetics relevant to interactions

• After intranasal dosing, rapid systemic and brain entry with high reported bioavailability and brief in vitro half‑life but prolonged CNS action suggests peak‑related pharmacodynamic interactions are most likely soon after dosing.

• Known, labeled contraindications or clinical drug–drug interactions for Selank were not identified in peer‑reviewed sources; clinical use should therefore default to precaution in pregnancy, lactation, pediatrics, and in individuals with potential peptide hypersensitivity. Mechanistic data support plausible pharmacodynamic interactions with CNS depressants/GABAergic agents, serotonergic and dopaminergic drugs, opioid agonists/antagonists, immunomodulatory therapies or vaccines, and anticoagulant/antiplatelet agents. Intranasal route factors may modify exposure in nasal mucosal disease. These inferences should be validated against local product information if available.

Toxicology#

We searched the accessible literature for toxicological information about Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro; TP‑7) focusing on LD50, organ toxicity, mutagenicity, and dose–response. The available peer‑reviewed sources retrieved provided dose–response and organ findings but did not report formal LD50 or genotoxicity study results.

LD50

• No LD50 values for Selank were located in the retrieved peer‑reviewed sources. A comprehensive review describing Selank’s pharmacology and development did not include LD50 data.

Organ toxicity studies

• Liver: In a rat model of drug‑induced (toxic) hepatitis produced by 21 days of isoniazid, rifampicin, and ethanol, Selank was administered once daily (intranasal, 0.2 mg/kg). Selank produced regression of pathological changes on histology (reduced inflammatory hyperaemia of inflow/outflow vessels and sinusoids; decreased sclerosis of arterial and portal branches; preserved lobular architecture; absence of hepatocyte degeneration/necrosis). Stereometric measures and clinical chemistry improved, with normalization of protein metabolism and lipid markers and restoration of hepatocyte area; Selank also enhanced regenerative features (hyperchromatic/binucleated hepatocytes). In this model, control mortality was 20%, whereas peptide treatment prevented lethality.
• Other organs: The retrieved sources did not report kidney or CNS histopathology consistent with organ toxicity. A review notes Selank showed prolonged effects without side effects in monkeys, but provides no organ histology.

Mutagenicity/genotoxicity

• No primary data for Ames, in vitro chromosomal aberration, or in vivo micronucleus tests for Selank were identified in the retrieved sources.

Dose–response relationships (quantitative)

• Rodent CNS/behavioral dosing: Reported active ranges include 30–50 μg/kg (shorter‑duration effects), 200–3000 μg/kg for anxiolytic activity in BALB/c mice (with strain‑dependence; little effect in C57BL/6), and repeated 1000–2000 μg/kg eliminating depressive‑like symptoms in WAG/Rij rats. These data reflect pharmacodynamic effects rather than toxicity thresholds.
• Disease model regimen: In the drug‑induced hepatitis model, daily intranasal 0.2 mg/kg Selank for 21 days improved liver biochemistry and histology and prevented model‑related mortality.
• NOAEL/LOAEL: Not reported in the retrieved sources. The review notes clinical development and use without listing dose‑limiting adverse effects, but formal NOAEL/LOAEL determinations are not provided.

Summary

• LD50: Not reported in the retrieved evidence.
• Organ toxicity: Available animal data show hepatoprotective effects with improved histology and clinical chemistry; no evidence of liver toxicity; no data found for kidney or CNS toxicity. A review notes lack of side effects in primates without organ pathology details.
• Mutagenicity: No Ames/micronucleus/chromosomal aberration data were identified in the retrieved literature.
• Dose–response: Behavioral efficacy across 30–3000 μg/kg (strain‑dependent) in rodents and 0.2 mg/kg/day for 21 days in a hepatitis model with beneficial effects; NOAEL/LOAEL not available.

Limitations

• Much of Selank’s preclinical and regulatory dossier appears to be in Russian‑language sources and product monographs that were not retrievable here; formal acute toxicity (LD50), GLP histopathology across organs, and standard genotoxicity assays may exist outside the accessible set. Future work should include targeted retrieval of Russian regulatory documents or manufacturer toxicology reports to fill these gaps.

Evidence Gaps#

• Human adverse event data is limited to anecdotal reports
• Systematic adverse event monitoring has not been conducted
• Drug interaction studies are incomplete
• Long-term safety profiles are unknown

Related Reading#

• Selank overview and research guide
• Selank dosing protocols
• Selank risks and legal status