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FGL

FGL is a synthetic 15-residue peptide copying the loop that the neural cell adhesion molecule (NCAM) uses to switch on FGFR1 growth-factor signalling. In rodents it has sharpened learning and memory, strengthened synaptic transmission, and protected hippocampal neurons against amyloid-beta, ischemia and injury. Its dimeric form cleared a single-dose phase 1 study in 24 healthy men and the announced Alzheimer's trial never followed, so every efficacy claim on this page is still an animal claim. Two findings sit against the promise: it lowered the seizure threshold in a kindling model, and it reduced neuron counts in uninjured brains.

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Nootropic

D-Serine

D-serine is the D-enantiomer of the amino acid serine and acts as a signaling molecule in the brain, where it serves as a co-agonist at the NMDA subtype of glutamate receptor. It is produced from L-serine by the enzyme serine racemase and is one of the more abundant D-amino acids in mammals, concentrated in regions such as the forebrain. Because NMDA receptors require a co-agonist alongside glutamate in order to open, glia-derived D-serine helps govern synaptic plasticity, learning, and memory; reduced D-serine signaling is central to the NMDA-hypofunction model of schizophrenia, in which serum levels are decreased, and it has also been investigated as an adjunct in major depression and as a predictor of response to ketamine.

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BDNF

LM22A-4

LM22A-4 is a rationally designed small-molecule mimetic of the loop-II domain of BDNF that activates the TrkB neurotrophin receptor, discovered by in-silico screening in the Longo and Massa labs. It is a foundational research tool for the BDNF/TrkB arm of the neuroplasticity pathway, with broad neuroprotective, remyelinating, and cognition-rescuing activity across rodent models; offering a drug-like way to probe signaling normally driven by a large neurotrophin.

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Nootropic

PQCA

A selective M1 positive allosteric modulator from Merck, used as the reference preclinical tool for the claim that boosting acetylcholine at M1 alone improves cognition without the gut effects of a cholinesterase inhibitor.

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Nootropic

T-495

A Takeda M1 positive allosteric modulator built deliberately weak at amplifying acetylcholine, made to test whether a low cooperativity ceiling is what separates a procognitive effect from cholinergic side effects.

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Nootropic

Tulrampator

Tulrampator (S-47445) is a selective positive allosteric modulator of AMPA-type glutamate receptors developed by Servier. Beyond acutely potentiating glutamatergic transmission, it upregulates BDNF and NT-3, activates the mTOR/CREB plasticity pathway, and rescues age-related deficits in hippocampal long-term potentiation and synaptic architecture in animals. It is the best-characterized modern AMPA-PAM and the only ampakine of its cohort to reach large Phase 2 human trials.

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