Encyclopedia

Semax is a synthetic heptapeptide analog of the ACTH(4-10) fragment, developed at the Institute of Molecular Genetics of the Russian Academy of Sciences. It is studied as a neuroprotective nootropic that upregulates the neurotrophins BDNF and NGF without stimulating cortisol. It is used clinically in Russia for some neurological indications but is not FDA-approved in the United States.

Semax has the sequence Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), built by appending a C-terminal Pro-Gly-Pro tripeptide to the ACTH(4-7) fragment to resist enzymatic degradation. Unlike full ACTH, it does not stimulate cortisol release. Preclinical and Russian clinical research has examined it for cognitive enhancement, stroke/ischemia neuroprotection, and attention, with proposed mechanisms centered on rapid upregulation of BDNF and its receptor TrkB in the hippocampus, modulation of nitric oxide and lipid peroxidation, and effects on monoaminergic signaling. In the U.S. it is sold as a research chemical (often as the more stable N-acetyl amidated derivative) and is among peptides under FDA 503A compounding review.

Mechanism of Action

Proposed to rapidly increase expression of BDNF and TrkB in the hippocampus, support neurotrophic/neuroprotective signaling, regulate cortical nitric oxide and lipid peroxidation, and modulate monoamine neurotransmitter systems. As an ACTH(4-10) analog it retains neurotropic activity without the corticotropic (cortisol-releasing) effect of full ACTH.