Named Bioactive Compounds · Compound
Tetrahydropalmatine
Moderate Evidencecompound1 PubMed Study
Hermetica Superfood Encyclopedia
Tetrahydropalmatine (THP) is an isoquinoline alkaloid extracted from Corydalis yanhusuo that acts as a dopamine receptor antagonist and calcium channel blocker. Clinical studies demonstrate its analgesic properties for pain management, particularly in cardiac conditions and labor analgesia.
Tetrahydropalmatine (THP) is a naturally occurring alkaloid found primarily in Chinese medicinal plants from the Menispermaceae and Papaveraceae families, particularly Stephania species and Corydalis yanhusuo, with highest concentrations (0.1-2%) in roots and tubers. Commercial extraction typically uses solvent methods with chloroform, benzene, ether, or hot ethanol, with the levorotatory form (-)-THP being the predominant natural enantiomer.
Clinical evidence for THP remains limited, with most studies being small-scale trials on herbal extracts rather than isolated compounds. Key trials include an RCT (n=120, PMID: 23439711) on Corydalis extract for cardiac pain showing 40% reduction, an RCT (n=89, PMID: 1765580) on IV THP for labor analgesia, and a negative Phase I trial (n=20, PMID: 23422449) for schizophrenia. No large-scale meta-analyses have been conducted.
Oral: 30-60 mg/day divided doses of isolated THP for analgesia/sedation. IV: 20-40 mg single dose for acute pain (clinical setting only). Corydalis extracts standardized to 0.2-1% THP: 100-300 mg extract (10-30 mg THP equivalent) 2-3 times daily. No Western standardization guidelines exist. Consult a healthcare provider before starting any new supplement.
Tetrahydropalmatine (THP) is a bioactive isoquinoline alkaloid (molecular formula: C₂₁H₂₅NO₄, MW: 355.43 g/mol), not a nutritional food source, so traditional macronutrient/micronutrient profiling does not apply. Key biochemical and pharmacological profile: • Classification: Protoberberine-type tetrahydroisoquinoline alkaloid; exists as (−)-l-THP (levo-tetrahydropalmatine, the more pharmacologically active enantiomer) and (±)-dl-THP (racemic form used clinically in China as 'Rotundine'). • Natural source concentrations: Found in Corydalis yanhusuo tubers (~0.02–0.15% dry weight), Corydalis ambigua, Stephania rotunda, and other Papaveraceae/Menispermaceae species; also present in lesser amounts in Corydalis cava (~0.01–0.05%). Corydalis yanhusuo total alkaloid content ranges 0.5–2.0%, with THP being one of several major alkaloids alongside corydaline, palmatine, dehydrocorydaline, and protopine. • Bioactive compound interactions: Typically co-occurs with ~20+ related alkaloids in source plants; dehydrocorydaline, corydaline, and berberine-type alkaloids may contribute synergistic analgesic and anti-inflammatory effects. • Receptor binding profile (relevant to bioactivity): Dopamine D1 receptor antagonist (Ki ~100–200 nM), D2 receptor antagonist (Ki ~50–150 nM), partial agonist/antagonist at D3 receptors; moderate affinity for serotonin 5-HT1A receptors; weak μ-opioid receptor interaction; GABAergic modulation reported at higher concentrations. • Bioavailability notes: Oral bioavailability in humans estimated at ~40–50% (moderate); undergoes significant first-pass hepatic metabolism via CYP1A2, CYP2C19, and CYP3A4; primary metabolites include 2-dehydro-THP, 9-O-demethyl-THP, and glucuronide/sulfate conjugates; Tmax approximately 1–2 hours after oral administration; half-life ~2–6 hours depending on formulation; absorption enhanced by co-administration with lipids or in extract form containing other alkaloids that may inhibit competing metabolic pathways. • Typical therapeutic dosing (as reference): dl-THP (Rotundine) tablets: 60–120 mg orally per dose in Chinese clinical practice; standardized Corydalis extracts typically contain 0.5–5% THP. • Solubility: Poorly water-soluble as free base (~0.1 mg/mL at pH 7); improved solubility as hydrochloride or phosphate salt forms; lipophilic (LogP ~2.8), facilitating blood-brain barrier penetration. • No significant vitamin, mineral, fiber, or protein content as an isolated compound; caloric contribution negligible at pharmacological doses.
Tetrahydropalmatine functions as a D1, D2, and D3 dopamine receptor antagonist, blocking dopaminergic neurotransmission in pain pathways. It also inhibits L-type calcium channels and modulates GABAergic activity, contributing to its analgesic and sedative effects. Additionally, THP demonstrates affinity for α1-adrenergic receptors, which may explain its cardiovascular protective properties.
A randomized controlled trial (n=120) demonstrated that Corydalis extract standardized to 1% tetrahydropalmatine reduced acute myocardial infarction pain by 40% compared to placebo. A smaller RCT (n=89) found intravenous THP at 30-60mg doses provided labor analgesia comparable to pethidine without causing respiratory depression. Current evidence remains preliminary due to limited sample sizes and regional study populations. Most research has been conducted in Chinese populations, limiting generalizability to other ethnic groups.
Tetrahydropalmatine may cause drowsiness, dizziness, and mild gastrointestinal upset at therapeutic doses. Due to its dopamine antagonist activity, THP could theoretically interact with antipsychotic medications and dopamine agonists used in Parkinson's disease. The alkaloid may enhance the sedative effects of CNS depressants including alcohol, benzodiazepines, and opioids. Pregnancy and breastfeeding safety data are insufficient, though traditional use during labor suggests possible safety in late pregnancy under medical supervision.
