ModafinilvsNALT

Modafinil's exact mechanism is not fully understood but involves multiple neurotransmitter systems. It inhibits the dopamine transporter (DAT) with moderate affinity, weakly increasing synaptic dopamine levels without causing vesicular depletion. Modafinil activates orexin/hypocretin neurons in the lateral hypothalamus—the brain's master wakefulness system—which project to histaminergic tuberomammillary nuclei, noradrenergic locus coeruleus, and cholinergic basal forebrain. This increases histamine release (promoting cortical arousal via H1 receptors), elevates norepinephrine in the prefrontal cortex (enhancing attention and executive function), and modulates serotonin (5-HT) transmission. Unlike amphetamines, it does not cause significant vesicular catecholamine release or reverse monoamine transporters, which explains its lower abuse potential and lack of typical stimulant crash.

NALT (N-acetyl L-tyrosine) is deacetylated by aryl acylamidase in the gut and liver to release L-Tyrosine. Tyrosine is hydroxylated to L-DOPA by tyrosine hydroxylase (TH) — the rate-limiting step in catecholamine synthesis, requiring tetrahydrobiopterin as cofactor. L-DOPA is decarboxylated by aromatic L-amino acid decarboxylase (AADC) to dopamine; dopamine is converted to norepinephrine by dopamine beta-hydroxylase (DBH), and norepinephrine to epinephrine by phenylethanolamine N-methyltransferase (PNMT). Under stress or sleep deprivation, catecholamine stores in noradrenergic and dopaminergic neurons deplete rapidly. Supplemental tyrosine provides substrate to maintain synthesis when demand exceeds supply, supporting prefrontal cortex function and working memory.