Semax Pharmacokinetics
Semax half-life, absorption, routes of administration, and clearance.
Intranasal-to-Brain Pharmacokinetics: Bypassing the Blood-Brain Barrier
Semax's pharmacokinetic profile is defined by a paradox: extremely short plasma half-life (minutes) yet prolonged CNS effects (hours to days). This disconnect is explained by intranasal delivery bypassing systemic circulation entirely.
Intranasal Absorption and CNS Penetration
The intranasal route delivers Semax directly to the brain via olfactory and trigeminal nerve pathways, achieving CNS concentrations impossible through systemic dosing. • Tritium-labeled Semax studies demonstrate peak brain concentrations within 30 minutes of intranasal administration, with detectable levels persisting in hippocampal and cortical tissue for 24+ hours. • Plasma half-life is approximately 2-3 minutes due to rapid enzymatic degradation by enkephalinase and carboxypeptidase. The Pro-Gly-Pro C-terminal extension provides partial protection against proteolysis but does not prevent systemic clearance. • Intranasal bioavailability to the CNS is estimated at 1-3% of the administered dose — low in absolute terms but sufficient for pharmacological effect because the target tissue (brain) receives drug directly without first-pass hepatic metabolism.
Physicochemical and PK profile
- Molecular Formula
- C37H51N9O10S
- Molecular Weight
- 813.93 g/mol
- CAS Number
- 80714-61-0
- Half-Life
- Several minutes in serum; CNS effects may persist longer
- Sequence
- Met-Glu-His-Phe-Pro-Gly-Pro
- Solubility
- Soluble in water
- Storage
- Store at -20°C. Nasal spray formulations may be stored at refrigerator temperatures.
References
- Semax, an ACTH(4-10) analogue, and brain BDNF expression · Dolotov OV, et al. · 2006
- Dergunova LV, Filippenkov IB, Stavchansky VV, et al. Novel insights into the protective properties of ACTH(4-7)PGP (Semax) peptide at the transcriptome level following cerebral ischaemia-reperfusion in rats. Genes (Basel). 2020;11(6):681. · Filippenkov IB, Stavchansky VV, Denisova AE, Yuzhakov VV, Sevan'kaeva LE, Sudarkina OY, Dmitrieva VG, Gubsky LV, Myasoedov NF, Limborska SA, Dergunova LV · 2020
- [Results of the application of complex physiotherapeutic neurostimulation in optical neuropathies of various genesis]. · Dragon AK, Korchazhkina NB, Sheludchenko VM et al. · 2022
- The peptide semax affects the expression of genes related to the ... · Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV · 2014
- Functional Connectomic Approach to Studying Selank and Semax Effects. · Panikratova YR, Lebedeva IS, Sokolov OY et al. · 2020
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- Shadrina MI, Dolotov OV, Grivennikov IA, et al. Comparison of the temporary dynamics of NGF and BDNF gene expression in rat hippocampus, frontal cortex, and retina under Semax action. J Mol Neurosci. 2010;41(1):30-35. · Shadrina M, Kolomin T, Agapova T, Agniullin Y, Shram S, Slominsky P, Lymborska S, Myasoedov N · 2010
- Effects of Semax on the Default Mode Network of the Brain. · Lebedeva IS, Panikratova YR, Sokolov OY et al. · 2018
- Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus · Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, Dubynina EV, Novosadova EV, Andreeva LA, Alfeeva LY, Kamensky AA, Grivennikov IA, Myasoedov NF, Engele J · 2006
- Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005;30(12):1493-1500. · Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS · 2005
- Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials. · Charland SL, Stanek EJ · 2014
- Kaplan AY, Kochetova AG, Nezavibathko VN, Rzhevskii DA, Roshchina IF, Ashmarin IP. Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome. Med Hypotheses. 2007;68(2):306-310. · Tsai SJ · 2007
- Diagnostic Value of Different 3-D Shear Wave Elastography Sections in the Diagnosis of Thyroid Nodules. · Hu Z, Lu M, Wang X et al. · 2022