Neuropeptides Selank & Semax

Selank and Semax are synthetic heptapeptides developed at the Russian Academy of Sciences' Institute of Molecular Genetics. Both append the C-terminal tripeptide Pro-Gly-Pro to a biologically active fragment of an endogenous peptide — a strategy that dramatically extends plasma stability beyond the seconds-long half-life of the parent sequences.

Semax — ACTH(4–10) Analog

Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic analog of the 4–10 fragment of adrenocorticotropic hormone (ACTH), with the Pro-Gly-Pro tail conferring resistance to proteolysis. Unlike native ACTH(4–10), Semax has no measurable corticotropic activity. Preclinical and clinical research has focused on:

• BDNF / NGF expression: Upregulation of brain-derived neurotrophic factor and nerve growth factor in the hippocampus and frontal cortex (Dolotov et al., Brain Res, 2006).
• Neuroprotection in ischemia: Reduction of infarct volume in rodent middle cerebral artery occlusion models; Semax is registered in Russia for acute ischemic stroke and transient ischemic attack.
• Cognition: Improvements in attention and memory tasks in studies of healthy adults and patients with cerebrovascular disease (Kaplan et al., Neurosci Behav Physiol, 1996).

Plasma half-life after intranasal dosing is short, on the order of minutes.

Selank — Tuftsin Analog

Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a synthetic analog of the immunomodulatory tetrapeptide tuftsin (Thr-Lys-Pro-Arg), again stabilized with Pro-Gly-Pro. Preclinical and clinical research has highlighted:

• Anxiolytic activity: Anxiolysis in elevated plus-maze and Vogel conflict tests at doses that do not produce sedation or motor impairment (Kozlovskaya et al., Eksp Klin Farmakol, 2003).
• GABAergic and serotonergic modulation: Changes in enkephalin degradation, GABA-A receptor signaling, and BDNF expression in the hippocampus.
• Clinical anxiety studies: Russian clinical trials reported non-inferiority to medazepam in generalized anxiety disorder without benzodiazepine-style withdrawal (Zozulya et al., Bull Exp Biol Med, 2008).

Shared Pharmacology

Both peptides are typically studied via intranasal administration, which provides a direct nose-to-brain route bypassing first-pass metabolism. Despite very short plasma half-lives, behavioral and neurochemical effects in animal models persist for hours, consistent with downstream neurotrophic and gene-expression changes rather than direct receptor occupancy.

Regulatory Status

Selank and Semax are registered medicinal products in the Russian Federation. Neither is approved by the US FDA, and high-quality randomized trials outside Russia remain limited. Both are sold strictly as reference compounds for in-vitro and preclinical laboratory research.

References

• Dolotov OV, et al. Semax, an analog of ACTH(4–10), regulates expression of immediate-early genes and BDNF in the rat brain. Brain Res. 2006;1117(1):54–60.
• Kaplan AYa, et al. Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neurosci Behav Physiol. 1996;26(5):425–430.
• Kozlovskaya MM, et al. Selank and short peptides of the tuftsin family in regulation of adaptive behavior. Eksp Klin Farmakol. 2003;66(5):3–6.
• Zozulya AA, et al. The efficacy of Selank in the therapy of anxiety disorders. Bull Exp Biol Med. 2008;146(4):457–460.