ALCARvsForskolin

ALCAR crosses the blood-brain barrier via the organic cation transporter (OCTN2) more effectively than L-carnitine. In neurons, it is hydrolyzed by carnitine acetyltransferase to donate its acetyl group to coenzyme A, forming acetyl-CoA—which can then be used for acetylcholine synthesis via choline acetyltransferase, effectively providing raw material for the memory neurotransmitter. ALCAR also transports long-chain fatty acids across the inner mitochondrial membrane via the carnitine palmitoyltransferase system for beta-oxidation and ATP production. ALCAR activates nerve growth factor (NGF) signaling, possibly through modulation of NGF receptor (TrkA) expression or downstream MAPK/ERK pathways. It has antioxidant properties, reducing lipid peroxidation in mitochondrial membranes and scavenging free radicals. These mechanisms support cognitive function and neuroprotection.

Forskolin directly activates all nine isoforms of membrane-bound adenylate cyclase (AC1-9), the enzyme that converts ATP to cyclic AMP (cAMP), bypassing G-protein-coupled receptor activation. Elevated cAMP activates protein kinase A (PKA), which phosphorylates CREB (cAMP response element-binding protein) at Ser133 — a transcription factor essential for long-term memory formation that induces expression of BDNF, c-fos, and other plasticity-related genes. This is the same signaling cascade used by dopamine (D1), norepinephrine (beta-adrenergic), and serotonin (5-HT4/7) receptors, but forskolin activates it directly at the effector level. Elevated cAMP also increases neurotransmitter receptor sensitivity (e.g., beta-adrenergic receptor phosphorylation), enhances synaptic plasticity via PKA-mediated GluA1 phosphorylation, and potentiates L-type calcium channels. Forskolin may also activate TRPV channels.