Harmaline

Harmaline (C₁₂H₁₂N₂O; MW 212.25 g/mol) is a dihydro-β-carboline alkaloid, not a nutritional substance per se, but a bioactive compound found naturally in specific plant sources. It has no macronutrient value (no protein, fat, carbohydrate, or fiber contribution at pharmacologically relevant doses). Key details: • Primary natural sources: Seeds of Peganum harmala (Syrian rue) containing ~2–7% total β-carboline alkaloids by dry weight, of which harmaline typically constitutes ~33–56% (approximately 1–4% of seed dry weight); also found in trace amounts in Banisteriopsis caapi vine bark (~0.03–0.08% dry weight, secondary to harmine). • Chemical class: 7-Methoxy-1-methyl-4,9-dihydro-3H-β-carboline; differs from harmine by saturation of the C-3,4 bond in the pyridine ring, resulting in distinct pharmacokinetic and potency profiles. • Bioactive concentration benchmarks: MAO-A inhibition IC₅₀ ~3–5 nM (reversible, competitive); MAO-B inhibition IC₅₀ ~100 µM (highly selective for MAO-A, selectivity ratio ~20,000–30,000-fold); acetylcholinesterase inhibition IC₅₀ ~30–50 µM (moderate). • Bioavailability notes: Oral bioavailability in rodent models estimated at ~20–50% due to significant first-pass hepatic metabolism; primary metabolic pathway is O-demethylation by CYP2D6 and CYP1A2 to harmol and harmalol, followed by glucuronidation and sulfation; plasma half-life approximately 1–3 hours in animal models; crosses the blood-brain barrier readily due to lipophilicity (LogP ~1.6–2.0). • Co-occurring bioactives in P. harmala seeds: Harmine (~2–5% dry weight), harmalol (~0.5–1%), tetrahydroharmine (trace), vasicine/deoxyvasicine (quinazoline alkaloids, ~0.5–1%), plus minor flavonoids and fatty acids in seed oil fraction. • Micronutrient context of whole P. harmala seeds (not harmaline isolate): Seeds contain minerals including potassium, calcium, magnesium, iron, and zinc in modest amounts, plus ~15–20% crude protein, ~10–15% lipid (linoleic and oleic acid predominant), and ~20–25% crude fiber, though these are nutritional properties of the seed matrix rather than harmaline itself. • Solubility: Sparingly soluble in water (~1.5 mg/mL at pH 7); enhanced solubility at acidic pH as hydrochloride salt (~50 mg/mL); freely soluble in ethanol, methanol, and DMSO. • Stability: Sensitive to light (UV degradation of the indole chromophore); relatively stable at acidic pH and under dark storage conditions at room temperature.