Mechanism-First Classification. This taxonomy organizes compounds by how they work rather than traditional categories. A compound’s primary biological mechanism determines its placement — enabling intelligent stacking decisions and avoiding redundancy.
Provide choline substrate for acetylcholine synthesis
Compound
Choline Yield
BBB
Unique Features
CDP-Choline (Citicoline)
18%
★★★★★
+Uridine → dopamine receptors
Alpha-GPC
40%
★★★★★
Highest yield; GH release
Phosphatidylcholine
13%
★★★☆☆
Membrane source
Choline Bitartrate
41%
★★☆☆☆
Poor CNS delivery
DMAE
Indirect
★★★☆☆
Controversial efficacy
NTRPX Application: CDP-Choline (SynaptiQ) for daily use in Boost/Sustain; Alpha-GPC (RapidChol) reserved for Sprint acute use to limit TMAO.
1.1.2 Acetylcholinesterase Inhibitors
Prevent ACh degradation, prolonging signaling
Compound
Potency
Selectivity
Duration
Notes
Huperzine A
High
AChE selective
10-14 h
Chinese club moss
Galantamine
Moderate
AChE + nAChR PAM
6-8 h
Dual mechanism
Rivastigmine
Moderate
AChE + BuChE
8-10 h
Pharmaceutical
Donepezil
High
AChE selective
70 h
Pharmaceutical
AChE inhibitors potentiate cholinergic signaling. Combine with choline donors cautiously — excessive cholinergic load can cause headaches, GI distress, and bradycardia.
Dopamine, Norepinephrine, Epinephrine synthesis and signaling
1.2.1 Precursors
Substrates for catecholamine biosynthesis
Compound
Pathway Position
Notes
L-Tyrosine
Tyrosine → L-DOPA
Rate may be TH-limited
L-Phenylalanine
Phenylalanine → Tyrosine
Essential amino acid
N-Acetyl-L-Tyrosine (NALT)
Same as tyrosine
Better solubility; debated efficacy
Mucuna pruriens (L-DOPA)
L-DOPA → Dopamine
Bypasses TH; peripheral conversion
1.2.2 Enzyme Cofactors
Required for catecholamine synthesis enzymes
Cofactor
Enzyme
Role
P5P (Vitamin B6)
AADC
DOPA → Dopamine
BH4 (Tetrahydrobiopterin)
TH, TPH
Rate-limiting cofactor
Iron
TH
Hydroxylation cofactor
Vitamin C
DBH
DA → Norepinephrine
SAMe
PNMT, COMT
Methylation reactions
Copper
DBH
Cofactor
1.2.3 Reuptake Modulators
Affect dopamine transporter (DAT) and norepinephrine transporter (NET)
Compound
Target
Potency
Notes
Sabroxy (Oroxylin A)
DAT
Moderate
Natural; Oroxylum indicum
Methylphenidate
DAT/NET
High
Pharmaceutical (Ritalin)
Modafinil
DAT (weak)
Low
+Histamine, orexin
Phenylpiracetam
DAT modulation
Low
Banned in sport
Bupropion
DAT/NET
Moderate
Pharmaceutical (Wellbutrin)
1.2.4 MAO Modulators
Affect monoamine oxidase (degradation enzyme)
Compound
Selectivity
Reversibility
Notes
Selegiline
MAO-B (low dose)
Irreversible
Pharmaceutical
Hordenine
MAO-B
Reversible
Short-acting; barley
Rhodiola rosea
MAO-A/B (mild)
Reversible
Adaptogen
β-Carbolines
MAO-A
Reversible
Serotonin syndrome risk
MAO inhibitors have significant drug and food interactions. Combining MAOIs with serotonergic compounds or tyramine-rich foods can cause hypertensive crisis or serotonin syndrome.
1.2.5 COMT Modulators
Affect catechol-O-methyltransferase (degradation)
Compound
Mechanism
Potency
Notes
Quercetin
COMT inhibition
Mild
Dietary flavonoid
EGCG
COMT inhibition
Mild
Green tea
Luteolin
COMT inhibition
Mild
Dietary flavonoid
Tolcapone
COMT inhibition
High
Pharmaceutical
COMT Val158Met polymorphism affects baseline COMT activity. “Warrior” (Val/Val) genotypes have higher COMT activity and may benefit more from COMT inhibition.
5-HTP should not be combined with SSRIs, MAOIs, or other serotonergic compounds due to serotonin syndrome risk. Always use with peripheral decarboxylase inhibitor (green tea EGCG) if chronic use.
Positive allosteric modulators (PAMs) at GABA-A receptor
Compound
Binding Site
Potency
Notes
Apigenin
Benzodiazepine
Mild
Chamomile; non-sedating
Magnolol/Honokiol
Benzodiazepine
Moderate
Magnolia bark
Baicalin
Benzodiazepine
Moderate
Skullcap
Valerian
β3 subunit
Mild
Valerenic acid
Lemon Balm
GABA-T inhibition
Mild
Rosmarinic acid
Kava
Multiple
Moderate
Hepatotoxicity concern
Alcohol
Multiple
High
Not a supplement
Benzodiazepines
Benzodiazepine
High
Pharmaceutical
NTRPX Application: Apigenin in Luna provides mild GABA-A modulation without sedation or dependence risk — ideal for sleep support alongside glycine and magnesium.
1.4.3 GABA-B Modulators
Compound
Action
Risk
Notes
Phenibut
Agonist
High dependence
Not recommended
Baclofen
Agonist
Moderate
Pharmaceutical
GHB
Agonist
High
Controlled substance
GABA-B agonists (Phenibut, GHB, Baclofen) carry significant dependence and withdrawal risks. Phenibut withdrawal can be life-threatening. These are NOT recommended for supplementation.
Block adenosine-induced drowsiness and dopamine suppression
Compound
A1 Ki (µM)
A2A Ki (µM)
Half-life
Character
Paraxanthine
33
18
3.1 h
Clean; no jitters
Caffeine
44
40
5-6 h
Most common
Theobromine
80+
80+
6-10 h
Mild; chocolate
Theophylline
14
22
8-9 h
Anxiogenic; avoid
Theacrine
Indirect
Indirect
20+ h
No tolerance
Dynamine
Indirect
Indirect
1-2 h
Rapid onset/offset
NTRPX Application: Paraxanthine (EnfinX) in ParaCaffeine provides 2.2x higher A2A affinity than caffeine with shorter half-life and no anxiogenic theophylline pathway.
Phosphocreatine shuttle for rapid ATP regeneration
Form
Purity
Solubility
Evidence
Creatine Monohydrate
99.9%
★★★☆☆
★★★★★ Gold standard
Creatine HCl
99%+
★★★★★
★★★☆☆ Limited
Buffered (Kre-Alkalyn)
Variable
★★★★☆
★★☆☆☆ No advantage
NTRPX Application: NeuroCreatine (3g) in Solar supports brain ATP buffering — cognitive benefits are most pronounced under stress, sleep deprivation, or in vegetarians.
Using This Taxonomy: When evaluating a new compound, first identify its primary biological mechanism, then locate it within the appropriate domain and category. This reveals potential synergies, redundancies, and contraindications with existing formulations.
