spec sheet11 rows
HT-0712 (betamilast) is a PDE4 inhibitor purpose-engineered to be a memory drug. Designed across Inflazyme, Helicon and Dart NeuroScience, it targets the CREB memory pathway with a wider therapeutic window than the notoriously emetic rolipram. In animals it selectively boosts long-term (not short-term) memory in normal and aged mice, and it reached Phase 2 testing in age-associated memory impairment, making it the most deliberately memory-focused candidate in the PDE4 class.
- Purpose-engineered to enhance the CREB long-term-memory pathway
- Single-dose restoration of contextual, trace and spatial memory in aged mice
- Designed for a wider therapeutic window than rolipram
- Reached Phase 2 in age-associated memory impairment
- It was engineered specifically as a memory drug, targeting the CREB pathway rather than being repurposed from another indication.
- In rodents it boosts long-term memory but not short-term memory, and follows an inverted-U dose curve where too much loses the effect.
- Its Phase 2 age-associated-memory-impairment trial completed in 2015 but never posted results.
Mechanism
A PDE4 inhibitor that raises , activates PKA and drives to switch on CREB-regulated memory genes, demonstrated in vivo in the aged . It was explicitly positioned for a better therapeutic window than rolipram. Its PDE4 subtype selectivity is not clearly established, so it is best treated as a pan-PDE4 inhibitor.
receptor fingerprint
PDE4Inhibits
Activates (downstream)
PKAActivates (downstream)
Increases (downstream)
Evidencehow good the literature is
Rodent evidence is strong: a single dose restored contextual, trace and spatial memory in aged mice and induced CREB target genes (c-Fos, Zif268, Bdnf), rescued the memory deficit in CBP+/- mice, and enhanced post-stroke motor recovery. Human evidence is inconclusive: a Phase 1 PET study (NCT01215552) was terminated, and a Phase 2 age-associated-memory-impairment trial (NCT02013310, PRIME, n=119) completed in January 2015 but posted no results, leaving human benefit undemonstrated.
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Reviews report a wider therapeutic window and better tolerability than rolipram, but PDE4-class GI liabilities still apply. The honest bottom line: the age-associated-memory-impairment Phase 2 trial completed with no posted results and the program did not advance, so its human safety and efficacy picture is incomplete.
History
Originated at Inflazyme as IPL-455903, then developed through Helicon Therapeutics and Dart NeuroScience as a dedicated memory-enhancement drug built around CREB biology. It progressed to a Phase 2 trial (PRIME) in age-associated memory impairment before development quietly ended without a published efficacy result.
Reputation
Something of a legend among nootropic followers as the CREB memory drug that came closest to purpose-built cognitive enhancement. Its reputation rests on compelling animal data and an ambitious clinical premise, tempered by the honest fact that it never demonstrated benefit in humans.
Subjective profileweighing the evidence above
The best-designed memory-specific PDE4 candidate in this set, with a strong rodent story and a completed human Phase 2 program. Honestly, though, no positive human efficacy was ever published and the program did not advance, so human benefit remains unproven.
Resources
This entry is here for reference.
Research
- 2003first citedA mouse model of Rubinstein-Taybi syndrome: defective long-term memory is ameliorated by inhibi…
- 2017most recentInvestigational phosphodiesterase inhibitors in phase I and phase II clinical trials for Alzhei…
- 1.The PDE4 inhibitor HT-0712 improves hippocampus-dependent memory in aged mice.
- 2.A mouse model of Rubinstein-Taybi syndrome: defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4.
- 3.A novel phosphodiesterase type 4 inhibitor, HT-0712, enhances rehabilitation-dependent motor recovery and cortical reorganization after focal cortical ischemia.
- 4.Investigational phosphodiesterase inhibitors in phase I and phase II clinical trials for Alzheimer's disease.
4 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Has HT-0712 been shown to improve human memory?
No. Its rodent data are strong, but the human Phase 2 trial posted no results and the program did not advance, so human benefit is unproven.
Why was it considered better than rolipram?
It was designed for a wider therapeutic window, aiming to keep the memory benefit while reducing rolipram's severe emetic liability.
Can I buy it?
No. It is a research compound with no disclosed human dose and no approval.
Notes and cautions
- PDE4-class GI liabilities still apply
- Inverted-U dose response: too high a dose loses the benefit
- No positive human efficacy ever published
- Research-only; not a consumer product