Cortexin vs Dihexa

Polypeptide bioregulator from bovine cortex; modulates neurotransmitter activity; activates GABA and dopamine systems; reduces excitotoxicity; stimulates neuronal repair

Cortexin is a polypeptide bioregulator derived from porcine cerebral cortex, used clinically in Russia and Eastern Europe as a neuroprotective and nootropic agent for stroke, traumatic brain injury, and chronic cerebrovascular disorders. It contains a complex mixture of tissue-specific neuropeptides, amino acids, and microelements proposed to support neuronal survival, reduce excitotoxic damage, and promote neurotrophic factor expression in injured brain tissue. Russian clinical trials have examined cortexin in acute ischemic stroke rehabilitation and other neurological conditions, with results suggesting potential benefit in functional recovery, though studies are predominantly published in Russian-language journals with limited methodological transparency by international standards. Cortexin is not FDA-approved; it is a licensed prescription drug in Russia and several post-Soviet states, where it has regulatory approval for neurological indications. Cortexin administration: in clinical settings where it is approved, cortexin is administered by intramuscular injection, typically as a 10 mg dose reconstituted in saline or procaine. Clinical courses in Russian practice involve daily injections over 10-day cycles, repeated 1–2 times per year for chronic neurological conditions. This administration pattern is common to several Russian polypeptide bioregulators, including cerebrolysin — another porcine-derived peptide mixture with a broader international clinical trial dataset — and cortagen, a cardiac-focus bioregulator from the same pharmacological class. Cortexin is the cerebral-cortex-specific member of this class; cortagen targets cardiovascular tissue, and thymalin targets thymic/immune tissue. Provider availability for cortexin outside Russia is limited compared to peptides with international regulatory approvals; it is occasionally carried by compounding pharmacies and specialized nootropic suppliers. The PeptideBase cognitive peptides directory lists verified providers who carry neuroprotective peptide compounds.

HGF/MET receptor potentiator; promotes new synapse formation; estimated 7 orders of magnitude more potent than BDNF in synaptogenesis models

Dihexa is a synthetic small peptide drug candidate developed at Washington State University, proposed to augment cognitive function through potentiation of hepatocyte growth factor (HGF) and MET receptor signaling, a pathway that supports synaptic formation and hippocampal neuroplasticity. The underlying AT4/IRAP receptor system, through which dihexa is proposed to act, has been shown in preclinical rodent studies to enhance long-term potentiation (LTP) in hippocampal tissue and support neuroplastic processes associated with memory formation. Preclinical models have demonstrated memory-enhancing effects following dihexa administration; however, no peer-reviewed human clinical trials have been published as of 2025 and the compound does not appear in indexed biomedical literature under its common name. Dihexa is a research compound with no regulatory approval of any kind; it is not an approved pharmaceutical, and no human safety or pharmacokinetic data has been established. Dihexa administration in research contexts: the compound has been studied in rodent models via oral, intranasal, and subcutaneous routes, with preclinical data suggesting intranasal delivery may offer efficient CNS access due to olfactory pathway absorption. Nasal spray formulations are available through some research compound suppliers on this basis, though the clinical translatability of rodent CNS delivery data to humans has not been established. Dihexa is structurally derived from angiotensin IV and shares the AT4/IRAP receptor pharmacology of its precursor compounds; it is sometimes compared to semax and other nootropic peptides in terms of proposed cognitive mechanism, though its HGF/MET-dependent mechanism is distinct from the ACTH-fragment or NGF-upregulating mechanisms of semax and selank. The cognitive enhancement peptide landscape — and provider availability for researched compounds in this space — is covered in the PeptideBase cognitive peptides directory.