Dihexa 10mg – 30 capsules

Dihexa 10 mg — 30 oral research capsules. Dihexa (N-hexanoic-Tyr-Ile-(6) aminohexanoic amide) is among the most strikingly potent synaptogenic molecules ever characterized in academic neuropharmacology. Developed in the laboratory of Joseph Harding at Washington State University as part of a program optimizing angiotensin-IV-derived neurotrophic peptides, Dihexa is approximately seven orders of magnitude (~10,000,000-fold) more potent than BDNF in inducing functional synaptogenesis between hippocampal neurons in vitro — a figure that, even discounted aggressively, places it in a category of its own. Its proposed primary mechanism is augmentation of hepatocyte growth factor / c-Met signaling, the same axis that drives neuronal repair after stroke and traumatic injury.

Research Overview

Dihexa is the most pharmacologically optimized member of the angiotensin-IV-derived neurotrophic peptide family — a research program initiated by the Harding group at Washington State University after the discovery that angiotensin IV itself enhances memory and synaptic plasticity in rodent models [1]. Successive structural modifications, principally to confer oral bioavailability and CNS penetration, produced Dihexa: an orally active, BBB-permeant peptidomimetic with no measurable angiotensin receptor activity but extraordinary synaptogenic potency [1,2]. In primary hippocampal neuron cultures, Dihexa induces formation of functional excitatory synapses at sub-femtomolar concentrations — making it approximately seven orders of magnitude more potent than BDNF and several orders of magnitude more potent than any other known synaptogenic molecule [1]. The proposed primary mechanism involves augmentation of hepatocyte growth factor (HGF) / c-Met receptor signaling, with downstream activation of MAPK, PI3K-Akt and the canonical synaptic-protein-synthesis machinery [2]. In aged rats with established scopolamine-induced or natural age-related memory deficits, oral Dihexa rescues spatial-memory performance to young-adult levels [3]. The compound has emerged as a flagship research tool in the synaptogenesis-driven approach to neurodegenerative disease.

Primary Research Areas

• Synaptogenesis pharmacology — approximately seven orders of magnitude more potent than BDNF in inducing functional synapse formation in hippocampal neuron cultures [1].
• HGF / c-Met receptor signaling — the principal proposed mechanism, providing a clean pharmacological probe of HGF-mediated neuronal repair pathways [2].
• Cognitive rescue in aged rodent models — restores spatial memory in aged rats and in scopolamine-induced cognitive deficit models at orally relevant doses [3].
• Alzheimer’s and age-related cognitive decline research — investigated as a synaptogenesis-based alternative to amyloid-clearance and AChE-inhibitor strategies [1,3].
• Stroke and TBI repair models — of interest in research on post-injury synaptic remodeling and functional recovery [2].

References

1. McCoy AT, Benoist CC, Wright JW, et al. Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents. J Pharmacol Exp Ther. 2013;344(1):141–154.
2. Benoist CC, Wright JW, Zhu M, et al. Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs. J Pharmacol Exp Ther. 2011;339(1):35–44.
3. Wright JW, Kawas LH, Harding JW. The development of small molecule angiotensin IV analogs to treat Alzheimer’s and Parkinson’s diseases. Prog Neurobiol. 2015;125:26–46.