Curine

Curine at a Glance

Curine — also written (−)-bebeerine or l-curine — is a bisbenzylisoquinoline (bisBIQ) alkaloid: two benzylisoquinoline halves fused through ether bridges into a single large molecule, C₃₆H₃₈N₂O₆, CAS 436-05-5 ^{32Reference 32PubChem · 2026Curine, CID 253793 — compound record (C₃₆H₃₈N₂O₆; CAS 436-05-5; synonyms (−)-bebeerine, l-curine)View study →}. It is the major alkaloid of Chondrodendron platyphyllum and one of the characterised alkaloids of abuta (Cissampelos pareira) — both Menispermaceae, the family that supplied the South American arrow poison curare ^{2,19Reference 2Ribeiro-Filho J et al. · 2014AnimalCurine inhibits mast cell-dependent responses in mice — animal modelView study →Reference 19Bala M et al. · 2019In vitroBioactive isoquinoline alkaloids from Cissampelos pareira — in vitroView study →}.

That family resemblance is the first thing to get right and the easiest thing to get wrong. Curine is chemically adjacent to tubocurarine, but curine is not curare and curine is not tubocurarine — and what has actually been measured for the molecule is not a neuromuscular blocker’s pharmacology. The next section deals with that directly, because the confusion is the single most common error made about this compound.

What curine has been shown to do, largely by Brazilian groups working with the purified alkaloid, is a calcium story. It blocks L-type voltage-gated Ca²⁺ channels in vascular smooth muscle, relaxes resistance arteries, stabilises mast cells, and damps eosinophil, neutrophil and macrophage activation — giving it a coherent antiallergic, anti-asthmatic and anti-inflammatory profile in mice at low oral doses ^{1,2,5,6,7Reference 1Ribeiro-Filho J et al. · 2013AnimalCurine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma — animal modelView study →Reference 2Ribeiro-Filho J et al. · 2014AnimalCurine inhibits mast cell-dependent responses in mice — animal modelView study →Reference 5Ribeiro-Filho J et al. · 2019AnimalCurine inhibits macrophage activation and neutrophil recruitment in a mouse model of lipopolysaccharide-induced inflammation — animal modelView study →Reference 6Medeiros MA et al. · 2011In vitroCurine, a bisbenzylisoquinoline alkaloid, blocks L-type Ca²⁺ channels and decreases intracellular Ca²⁺ transients in A7r5 cells — in vitroView study →Reference 7Dias CS et al. · 2002AnimalMechanisms involved in the vasodilator effect of curine in rat resistance arteries — ratsView study →}. It is also a genuine antiprotozoal in vivo ^{12,14Reference 12Fournet A et al. · 1997AnimalThe effect of bisbenzylisoquinoline alkaloids on Trypanosoma cruzi infections in mice — animal modelView study →Reference 14Mambu L et al. · 2000In vitroSpectral characterisation and antiplasmodial activity of bisbenzylisoquinolines from Isolona ghesquiereina — in vitro and in vivoView study →}. Every one of those findings is preclinical: no human has ever been given curine in a published study.

Curine, Curare & Tubocurarine

Three things get run together here, and they are three different kinds of thing.

Curare is a preparation, not a molecule. It is a crude plant arrow-poison — a mixture of many alkaloids from Menispermaceae and other families — and no single compound “is” curare. The famous molecule extracted from it is tubocurarine ^{22Reference 22Otto N et al. · 2017A modular access to (±)-tubocurine and (±)-curine — formal total synthesis of tubocurarineView study →}.

Curine is not tubocurarine. Curine and tubocurine are close chemical relatives that share the molecular formula C₃₆H₃₈N₂O₆ ^{32Reference 32PubChem · 2026Curine, CID 253793 — compound record (C₃₆H₃₈N₂O₆; CAS 436-05-5; synonyms (−)-bebeerine, l-curine)View study →}, and the 2017 synthetic route to the curare alkaloids reached (±)-tubocurine and (±)-curine through the same sequence — which is why making tubocurine constituted a formal total synthesis of tubocurarine ^{22Reference 22Otto N et al. · 2017A modular access to (±)-tubocurine and (±)-curine — formal total synthesis of tubocurarineView study →}. But tubocurarine itself is a different substance: the quaternary N-methylated cation, C₃₇H₄₁N₂O₆⁺, carrying a permanent positive charge ^{33Reference 33PubChem · 2026Tubocurarine, CID 6000 — compound record (C₃₇H₄₁N₂O₆⁺)View study →}. Curine is a tertiary base. That charge difference is not cosmetic — it is most of the reason tubocurarine is a potent nicotinic blocker.

What has actually been measured for curine at the neuromuscular junction. One study did look, under the synonym l-bebeerine, in rat diaphragm and toad sartorius muscle ^{8Reference 8Souccar C et al. · 1999AnimalNatural probes for cholinergic sites: L-bebeerine actions on the neuromuscular transmission, the nicotinic receptor/ionic channel complex, and contraction of skeletal muscles — ratsView study →}. It found real activity — and it is worth reading the numbers rather than the headline. Injected intraperitoneally at 0.05–1 g/kg, curine caused dose-related flaccid paralysis in rats, with respiratory arrest at the top of that range. In isolated muscle it depressed indirectly elicited twitches with an IC50 of 228 µM in rat diaphragm (5.4 µM in toad sartorius), reduced α-bungarotoxin binding to the junctional ACh receptor (IC50 47.7 µM), and blocked transmission non-competitively — the block was not reversed by neostigmine, which is not the competitive, anticholinesterase-reversible mechanism the classic curare blocker is named for. At 170–340 µM it also produced a muscle contracture unrelated to junctional block ^{8Reference 8Souccar C et al. · 1999AnimalNatural probes for cholinergic sites: L-bebeerine actions on the neuromuscular transmission, the nicotinic receptor/ionic channel complex, and contraction of skeletal muscles — ratsView study →}.

So: curine can paralyse, at gram-per-kilogram injected doses. Its anti-allergic effects appear orally at around 0.8 mg/kg ^{3Reference 3Ribeiro-Filho J et al. · 2015ReviewAnti-allergic properties of curine, a bisbenzylisoquinoline alkaloid — reviewView study →} — three orders of magnitude lower. The neuromuscular finding is a safety ceiling, not a therapeutic mechanism, and it should not be cited as evidence that curine “works like curare.”

The curarizing chemistry lives in curine’s derivatives, not in curine. Quaternise the nitrogens and you get compounds that genuinely are neuromuscular blockers: dimethyl-l-curine dimethochloride was developed in China and studied as an alternative to d-tubocurarine chloride, with its own mode-of-action work on neuromuscular transmission ^{23,24Reference 23Wu J · 1987Dimethyl-l-curine dimethochloride — an alternative for d-tubocurarine chlorideView study →Reference 24Yang QZ · 1981Yang QZ, Lin LR (1981). [Mode of action of dimethyl l-curine dimethochloride on neuromuscular transmission]. Acta Pharmacologica Sinica. https://pubmed.ncbi.nlm.nih.gov/6278828/View study →}; and alkylated bebeerine derivatives were investigated for curarizing activity in the 1960s, with O-methyl-N-methyl bebeerine (“kondrocurare”) reported in anaesthesia as early as 1952 ^{25,26Reference 25Zanini AC · 1963Zanini AC, Ramos AO (1963). [On the curarizing activity of alkylated derivatives of bebeerine]. Revista Brasileira de Biologia. https://pubmed.ncbi.nlm.nih.gov/14060694/View study →Reference 26Soares Bairão G · 1952Soares Bairão G, Cromberg S (1952). [O-methyl-N-methyl bebeerine (kondrocurare); its use in anesthesia] — clinical use report. Anesthésie et Analgésie. https://pubmed.ncbi.nlm.nih.gov/14952850/View study →}. Those are made molecules. The native alkaloid is not one of them.

What It's Used For

The research base is modest in volume but unusually coherent: almost all of it uses the isolated alkaloid, and almost all of it converges on calcium handling.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. There is no human evidence for any row, so every score is capped low by design.

01Allergic asthma / antiallergicShaky42%Oral isolate in mouse OVA asthma + mast-cell models, mechanism-matched to verapamil ^{1,2,3Reference 1Ribeiro-Filho J et al. · 2013AnimalCurine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma — animal modelView study →Reference 2Ribeiro-Filho J et al. · 2014AnimalCurine inhibits mast cell-dependent responses in mice — animal modelView study →Reference 3Ribeiro-Filho J et al. · 2015ReviewAnti-allergic properties of curine, a bisbenzylisoquinoline alkaloid — reviewView study →}

02Anti-inflammatory / analgesicShaky38%Mouse pleurisy, oedema, writhing, hyperalgesia; PGE₂ and macrophage cytokine suppression ^{4,5Reference 4Leite FC et al. · 2014AnimalCurine, an alkaloid isolated from Chondrodendron platyphyllum, inhibits prostaglandin E2 in experimental models of inflammation and pain — miceView study →Reference 5Ribeiro-Filho J et al. · 2019AnimalCurine inhibits macrophage activation and neutrophil recruitment in a mouse model of lipopolysaccharide-induced inflammation — animal modelView study →}

03Vasorelaxation / calcium-channel blockadeShaky32%Rat artery myography + A7r5 patch clamp; no in-vivo haemodynamics ^{6,7Reference 6Medeiros MA et al. · 2011In vitroCurine, a bisbenzylisoquinoline alkaloid, blocks L-type Ca²⁺ channels and decreases intracellular Ca²⁺ transients in A7r5 cells — in vitroView study →Reference 7Dias CS et al. · 2002AnimalMechanisms involved in the vasodilator effect of curine in rat resistance arteries — ratsView study →}

04Antiparasitic / antiprotozoalShaky30%Oral cure of T. cruzi parasitaemia in mice; in-vitro T. brucei and Plasmodium activity ^{12,13,14,16Reference 12Fournet A et al. · 1997AnimalThe effect of bisbenzylisoquinoline alkaloids on Trypanosoma cruzi infections in mice — animal modelView study →Reference 13Fournet A et al. · 1998In vitroTrypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase — in vitroView study →Reference 14Mambu L et al. · 2000In vitroSpectral characterisation and antiplasmodial activity of bisbenzylisoquinolines from Isolona ghesquiereina — in vitro and in vivoView study →Reference 16Ali S et al. · 2020In vitroEffect of temperature on ¹H NMR spectra, antitrypanosomal activity, conformational analysis, and molecular docking of curine derivatives from Berberis brevissima — in vitroView study →}

05Cytotoxicity / anticancerShaky20%Cell lines only — leukaemia and hepatocellular carcinoma, low-µM ^{10,11Reference 10Dantas BB et al. · 2015In vitroEffects of curine in HL-60 leukemic cells: cell cycle arrest and apoptosis induction — in vitroView study →Reference 11Gong S et al. · 2017In vitroGong S, et al. (2017). (−)-Curine induces cell cycle arrest and cell death in hepatocellular carcinoma cells in a p53-independent way — in vitro. Biomedicine & Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/28292017/View study →}

Mechanisms

The load-bearing point: everything above the neuromuscular row is Ca²⁺-handling pharmacology measured on the isolate. The nicotinic row exists, is real, and belongs to a dose range three orders of magnitude above the effective one — read it under Toxicity, not as a mechanism of benefit.

Pharmacokinetics

There is no measured human pharmacokinetic dataset for curine — and no measured animal one either. The bisBIQ review that includes curine among thirteen representative alkaloids derives its ADME picture for these compounds from software prediction (ACD/Percepta), reporting the class as strongly P-glycoprotein-interacting, poorly absorbed orally, and strongly plasma-protein-bound, with a metabolic concern around quinone-methide formation linked to renal and hepatic toxicity ^{17Reference 17Zhang H et al. · 2021ReviewThirteen bisbenzylisoquinoline alkaloids in five Chinese medicinal plants: botany, traditional uses, phytochemistry, pharmacokinetic and toxicity studies — reviewView study →}. Those are class-level predictions, not curine measurements, and should be labelled as such.

The one directly measured transporter datum runs slightly against the prediction: curine is a weak inhibitor of rat Abcb1b-mediated rhodamine efflux, though it competes with verapamil at the pump ^{18Reference 18Sergent JA et al. · 2022In vitroEffects of two natural bisbenzylisoquinolines, curine and guattegaumerine, extracted from Isolona hexaloba, on rhodamine efflux by Abcb1b from rat glycocholic-acid-resistant hepatocarcinoma cells — in vitroView study →}. And the prediction of poor oral absorption sits awkwardly with the fact that curine is repeatedly orally active in rodents at low mg/kg — an ED50 near 0.8 mg/kg in the asthma model ^{3Reference 3Ribeiro-Filho J et al. · 2015ReviewAnti-allergic properties of curine, a bisbenzylisoquinoline alkaloid — reviewView study →} and 10 mg/kg/day clearing T. cruzi parasitaemia ^{12Reference 12Fournet A et al. · 1997AnimalThe effect of bisbenzylisoquinoline alkaloids on Trypanosoma cruzi infections in mice — animal modelView study →}. Whatever the absolute bioavailability, enough of it reaches the target.

No half-life, Cmax, volume of distribution, metabolite identity or route of excretion has been reported for curine in any species. This is the single largest hole in the molecule’s file.

Clinical Trials

None. Curine has never been administered to a human being in a published study, in any indication, at any dose. Every finding here is cell-culture, isolated-tissue or rodent work. The nearest thing to human exposure in this chemical lineage is not curine at all but its quaternised derivatives, used as neuromuscular blockers in anaesthesia ^{23,26Reference 23Wu J · 1987Dimethyl-l-curine dimethochloride — an alternative for d-tubocurarine chlorideView study →Reference 26Soares Bairão G · 1952Soares Bairão G, Cromberg S (1952). [O-methyl-N-methyl bebeerine (kondrocurare); its use in anesthesia] — clinical use report. Anesthésie et Analgésie. https://pubmed.ncbi.nlm.nih.gov/14952850/View study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

This molecule is unusually clean on this axis: nearly every result here is for the purified alkaloid, not an extract ^{1,2,4,5,6,7,10,11,12,13,14,16Reference 1Ribeiro-Filho J et al. · 2013AnimalCurine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma — animal modelView study →Reference 2Ribeiro-Filho J et al. · 2014AnimalCurine inhibits mast cell-dependent responses in mice — animal modelView study →Reference 4Leite FC et al. · 2014AnimalCurine, an alkaloid isolated from Chondrodendron platyphyllum, inhibits prostaglandin E2 in experimental models of inflammation and pain — miceView study →Reference 5Ribeiro-Filho J et al. · 2019AnimalCurine inhibits macrophage activation and neutrophil recruitment in a mouse model of lipopolysaccharide-induced inflammation — animal modelView study →Reference 6Medeiros MA et al. · 2011In vitroCurine, a bisbenzylisoquinoline alkaloid, blocks L-type Ca²⁺ channels and decreases intracellular Ca²⁺ transients in A7r5 cells — in vitroView study →Reference 7Dias CS et al. · 2002AnimalMechanisms involved in the vasodilator effect of curine in rat resistance arteries — ratsView study →Reference 10Dantas BB et al. · 2015In vitroEffects of curine in HL-60 leukemic cells: cell cycle arrest and apoptosis induction — in vitroView study →Reference 11Gong S et al. · 2017In vitroGong S, et al. (2017). (−)-Curine induces cell cycle arrest and cell death in hepatocellular carcinoma cells in a p53-independent way — in vitro. Biomedicine & Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/28292017/View study →Reference 12Fournet A et al. · 1997AnimalThe effect of bisbenzylisoquinoline alkaloids on Trypanosoma cruzi infections in mice — animal modelView study →Reference 13Fournet A et al. · 1998In vitroTrypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase — in vitroView study →Reference 14Mambu L et al. · 2000In vitroSpectral characterisation and antiplasmodial activity of bisbenzylisoquinolines from Isolona ghesquiereina — in vitro and in vivoView study →Reference 16Ali S et al. · 2020In vitroEffect of temperature on ¹H NMR spectra, antitrypanosomal activity, conformational analysis, and molecular docking of curine derivatives from Berberis brevissima — in vitroView study →}. That is a genuine strength — the calcium-channel block, the mast-cell stabilisation and the oral anti-asthmatic effect are properties of curine, not of a mixture that happens to contain it. The isolate was sourced from different plants in different labs: Chondrodendron platyphyllum roots for the Brazilian antiallergic and anti-inflammatory series ^{2,4Reference 2Ribeiro-Filho J et al. · 2014AnimalCurine inhibits mast cell-dependent responses in mice — animal modelView study →Reference 4Leite FC et al. · 2014AnimalCurine, an alkaloid isolated from Chondrodendron platyphyllum, inhibits prostaglandin E2 in experimental models of inflammation and pain — miceView study →}, Cyclea wattii roots for the hepatocellular-carcinoma work ^{11,20Reference 11Gong S et al. · 2017In vitroGong S, et al. (2017). (−)-Curine induces cell cycle arrest and cell death in hepatocellular carcinoma cells in a p53-independent way — in vitro. Biomedicine & Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/28292017/View study →Reference 20Wang JZ et al. · 2010In vitroTwo new curine-type bisbenzylisoquinoline alkaloids from the roots of Cyclea wattii with cytotoxic activities — in vitroView study →}, Isolona species for the antiplasmodial and P-gp studies ^{14,18Reference 14Mambu L et al. · 2000In vitroSpectral characterisation and antiplasmodial activity of bisbenzylisoquinolines from Isolona ghesquiereina — in vitro and in vivoView study →Reference 18Sergent JA et al. · 2022In vitroEffects of two natural bisbenzylisoquinolines, curine and guattegaumerine, extracted from Isolona hexaloba, on rhodamine efflux by Abcb1b from rat glycocholic-acid-resistant hepatocarcinoma cells — in vitroView study →}, and Berberis brevissima roots for the antitrypanosomal MIC ^{16Reference 16Ali S et al. · 2020In vitroEffect of temperature on ¹H NMR spectra, antitrypanosomal activity, conformational analysis, and molecular docking of curine derivatives from Berberis brevissima — in vitroView study →}.

The transferability problem runs in the opposite direction to the usual one. Because the human-facing herb here is abuta, and abuta root contains curine only as one member of a bisbenzylisoquinoline mixture alongside hayatinine, cycleanine, tetrandrine, magnocurarine and the aporphine magnoflorine ^{19Reference 19Bala M et al. · 2019In vitroBioactive isoquinoline alkaloids from Cissampelos pareira — in vitroView study →}, a curine result cannot be read as an abuta result — and abuta’s traditional uses cannot be credited to curine. In the same alkaloid screen, curine was not the most cytotoxic member of the group; hayatinine and cycleanine were ^{19Reference 19Bala M et al. · 2019In vitroBioactive isoquinoline alkaloids from Cissampelos pareira — in vitroView study →}.

Prevalence in Nature

Curine is a Menispermaceae alkaloid first and foremost, but it is not confined to that family.

Menispermaceae. It is described as the major constituent isolated from Chondrodendron platyphyllum, a northeastern-Brazilian vine known locally as “abútua” ^{2,3,4Reference 2Ribeiro-Filho J et al. · 2014AnimalCurine inhibits mast cell-dependent responses in mice — animal modelView study →Reference 3Ribeiro-Filho J et al. · 2015ReviewAnti-allergic properties of curine, a bisbenzylisoquinoline alkaloid — reviewView study →Reference 4Leite FC et al. · 2014AnimalCurine, an alkaloid isolated from Chondrodendron platyphyllum, inhibits prostaglandin E2 in experimental models of inflammation and pain — miceView study →}. In Cissampelos pareira — the abuta of this database — curine is one of the alkaloids isolated and quantified by a dedicated UPLC method alongside magnoflorine, magnocurarine, cissamine and hayatinine, with alkaloid content highest during the rainy season ^{19Reference 19Bala M et al. · 2019In vitroBioactive isoquinoline alkaloids from Cissampelos pareira — in vitroView study →}. It also occurs in Cyclea wattii roots as (−)-curine, from which two further curine-type alkaloids (wattisines A and B) were described ^{11,20Reference 11Gong S et al. · 2017In vitroGong S, et al. (2017). (−)-Curine induces cell cycle arrest and cell death in hepatocellular carcinoma cells in a p53-independent way — in vitro. Biomedicine & Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/28292017/View study →Reference 20Wang JZ et al. · 2010In vitroTwo new curine-type bisbenzylisoquinoline alkaloids from the roots of Cyclea wattii with cytotoxic activities — in vitroView study →}.

Beyond Menispermaceae. Curine has been isolated from the Annonaceae — the stem bark of Isolona ghesquiereina ^{14Reference 14Mambu L et al. · 2000In vitroSpectral characterisation and antiplasmodial activity of bisbenzylisoquinolines from Isolona ghesquiereina — in vitro and in vivoView study →} and the roots of Isolona hexaloba ^{18Reference 18Sergent JA et al. · 2022In vitroEffects of two natural bisbenzylisoquinolines, curine and guattegaumerine, extracted from Isolona hexaloba, on rhodamine efflux by Abcb1b from rat glycocholic-acid-resistant hepatocarcinoma cells — in vitroView study →} — and from the Berberidaceae, in the ethanolic root extract of Berberis brevissima ^{16Reference 16Ali S et al. · 2020In vitroEffect of temperature on ¹H NMR spectra, antitrypanosomal activity, conformational analysis, and molecular docking of curine derivatives from Berberis brevissima — in vitroView study →}. Some relatives make close analogues rather than curine itself: the stem bark and wood of Abuta grandifolia yielded O-methyl and O-demethyl curine derivatives (new compounds at the time), not the parent alkaloid ^{21Reference 21Cometa MF et al. · 2012In vitroNew cholinesterase inhibiting bisbenzylisoquinoline alkaloids from Abuta grandifolia — in vitroView study →}.

The historical outlier. The name bebeerine comes from the bark and wood of the greenheart tree (Nectandra rodiaei, Lauraceae) of British Guiana, whose alkaloids were worked on through the nineteenth century ^{27,28Reference 27Maclagan D · 1845On the medicinal properties of bebeerine — historical reportView study →Reference 28Blair D · 1847Facts and observations on the antiperiodic powers of bebeerine, in a report addressed to the Government Secretary of British Guiana — historical reportView study →} — a different family entirely, and one whose exact relationship to the modern molecule was contested for a hundred years (see below).

No quantified figure exists. Despite the seasonal-variation study, no published % dry weight for curine in any source plant was located. That is a hole, not an absence of the compound.

Discovery & Synthesis

Curine reached medicine long before it was properly identified, and under a different name. From the 1840s, British physicians working in British Guiana reported the sulphate of bebeerine — from greenheart bark — as an antiperiodic and a substitute for quinine in fevers, and its medicinal properties, antiperiodic powers and use in other conditions were argued over in the Edinburgh and American medical press across the following decade ^{27,28,29Reference 27Maclagan D · 1845On the medicinal properties of bebeerine — historical reportView study →Reference 28Blair D · 1847Facts and observations on the antiperiodic powers of bebeerine, in a report addressed to the Government Secretary of British Guiana — historical reportView study →Reference 29Dailey ED · 1853On the use of sulphate of bebeerine as a substitute for sulphate of quinia — historical reportView study →}. Maclagan and Gamgee later published the chemical characterisation of the greenheart alkaloids ^{30Reference 30Maclagan D · 1869On the alkaloids contained in the wood of the bebeeru or greenheart tree (Nectandra rodiœi, Schomb.)View study →}.

The identity stayed unstable for over a century. “Bebeerine” as sold was a variably-defined alkaloid preparation rather than a pure compound, and the composition of commercial bebeerine hydrochlorate was still being re-examined by Japanese alkaloid chemists as late as 1963 ^{31Reference 31Tomita M et al. · 1963Tomita M, Fujitani K, Kishimoto T (1963). [Studies on the alkaloids of menispermaceous plants. 194. On the “bebeerine hydrochlorate” (E. Merck)]. Yakugaku Zasshi. https://pubmed.ncbi.nlm.nih.gov/13985430/View study →}. Modern chemistry resolves it: curine is specifically the levorotatory isomer, (−)-bebeerine, C₃₆H₃₈N₂O₆, CAS 436-05-5 ^{32Reference 32PubChem · 2026Curine, CID 253793 — compound record (C₃₆H₃₈N₂O₆; CAS 436-05-5; synonyms (−)-bebeerine, l-curine)View study →}. Where an old source says “bebeerine” without specifying rotation, it is not safe to assume it means this molecule.

First total synthesis: 2017. Otto, Ferenc and Opatz reported the first successful synthetic entry to the curare alkaloids (±)-tubocurine and (±)-curine, built on two consecutive copper-catalysed Ullmann-type C–O couplings — 15 linear steps and 24 transformations from vanillin. Because tubocurine is one methylation from tubocurarine, that work also constituted a formal total synthesis of tubocurarine ^{22Reference 22Otto N et al. · 2017A modular access to (±)-tubocurine and (±)-curine — formal total synthesis of tubocurarineView study →}.

Manufacture today: none at scale. There is no commercial curine product. Every study cited here prepared the compound by research-scale isolation from plant roots, bark or wood; the 2017 synthesis is a laboratory route, not a production one.

Patents: not yet researched.

Toxicity & Safety

Curine carries a moderate flag. The reasoning is specific: at the doses where it works, the studies that looked for toxicity found none — but the molecule demonstrably blocks skeletal-muscle neuromuscular transmission, cardiac-relevant L-type calcium current and neuronal sodium channels, and it belongs to an alkaloid class with recognised renal and hepatic concerns. That is a real liability profile with a wide margin, not a benign phytochemical.

Safety at a Glance

⚠️ Moderate toxicityNeuromuscular cautionCardiac cautionDrug interactions

• No toxicity signal at effective doses. Seven days of oral curine at up to ten times the effective dose caused no haematological, biochemical, behavioural or physical changes in mice, and no gastric ulceration.
• It does block neuromuscular transmission — at enormous doses. Injected at 0.05–1 g/kg in rats it produced flaccid paralysis and, at the top of the range, respiratory arrest. The block is non-competitive and not reversed by neostigmine
• Real ion-channel activity. L-type Ca²⁺ block plus hNav1.2/hNav1.6 block below 10 µM — additive effects with calcium-channel blockers, antihypertensives, antiarrhythmics or sodium-channel-active drugs are plausible and unstudied.
• Class-level metabolic concern. Bisbenzylisoquinoline alkaloids are associated with quinone-methide formation and consequent renal and hepatic toxicity; no curine-specific organ-toxicity study exists.
• P-glycoprotein interaction. Curine competes with verapamil at ABCB1, a plausible transporter-level interaction route — weak in the one assay that measured it, unquantified in humans.
• Zero human exposure data. Nothing about tolerability, dose-limiting effects or interactions in people is known.

Full Safety & Interactions Detail

Why moderate and not low. The reassuring data are real: in the asthma study, a formal toxicological evaluation found that orally administered curine did not significantly alter biochemical, haematological, behavioural or physical parameters versus saline controls, and repeat oral dosing for seven consecutive days at up to ten times the ED50 produced no haematological or biochemical change and no gastric ulcers ^{1,3Reference 1Ribeiro-Filho J et al. · 2013AnimalCurine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma — animal modelView study →Reference 3Ribeiro-Filho J et al. · 2015ReviewAnti-allergic properties of curine, a bisbenzylisoquinoline alkaloid — reviewView study →}. But three findings keep it above low. First, the neuromuscular block is demonstrated for the molecule itself, not inferred from its family: dose-related flaccid paralysis and respiratory arrest in rats at 0.05–1 g/kg i.p., non-competitive junctional block not reversed by neostigmine, reduced α-bungarotoxin binding, plus a separate muscle contracture at 170–340 µM that intensified with temperature ^{8Reference 8Souccar C et al. · 1999AnimalNatural probes for cholinergic sites: L-bebeerine actions on the neuromuscular transmission, the nicotinic receptor/ionic channel complex, and contraction of skeletal muscles — ratsView study →}. Second, it is cardiovascularly active by design — an L-type Ca²⁺-channel blocker that relaxes resistance arteries at single-digit µM ^{6,7Reference 6Medeiros MA et al. · 2011In vitroCurine, a bisbenzylisoquinoline alkaloid, blocks L-type Ca²⁺ channels and decreases intracellular Ca²⁺ transients in A7r5 cells — in vitroView study →Reference 7Dias CS et al. · 2002AnimalMechanisms involved in the vasodilator effect of curine in rat resistance arteries — ratsView study →} — and additionally blocks neuronal sodium channels below 10 µM ^{9Reference 9Coquerel Q et al. · 2022In vitroScreening an in-house isoquinoline alkaloids library for new blockers of voltage-gated Na⁺ channels using voltage sensor fluorescent probes: hits and biases — in vitroView study →}. Third, the bisBIQ class carries documented renal and hepatic toxicity attributed to quinone-methide metabolites, and curine is explicitly one of the thirteen alkaloids reviewed under that heading ^{17Reference 17Zhang H et al. · 2021ReviewThirteen bisbenzylisoquinoline alkaloids in five Chinese medicinal plants: botany, traditional uses, phytochemistry, pharmacokinetic and toxicity studies — reviewView study →}.

Interactions (all theoretical — none studied). The named transporter is P-glycoprotein / ABCB1: curine competes with verapamil at the efflux pump, weakly in the one direct assay ^{18Reference 18Sergent JA et al. · 2022In vitroEffects of two natural bisbenzylisoquinolines, curine and guattegaumerine, extracted from Isolona hexaloba, on rhodamine efflux by Abcb1b from rat glycocholic-acid-resistant hepatocarcinoma cells — in vitroView study →}, and the class is predicted to interact strongly with P-gp ^{17Reference 17Zhang H et al. · 2021ReviewThirteen bisbenzylisoquinoline alkaloids in five Chinese medicinal plants: botany, traditional uses, phytochemistry, pharmacokinetic and toxicity studies — reviewView study →} — the plausible route to raised exposure of P-gp substrates. No CYP450 isoform data exist for curine at all, so hepatic-enzyme interactions are simply uncharacterised rather than absent. Pharmacodynamically, additive hypotension with calcium-channel blockers or antihypertensives, and additive effects with neuromuscular-blocking agents, sedatives or sodium-channel-active drugs, follow directly from the mechanisms above and should be treated as live possibilities.

Reproductive note (prose only). No reproductive or developmental-toxicity study of isolated curine was located. Abuta, one of its source plants, carries antifertility associations at the whole-plant level, which say nothing about the isolate. Pregnancy and lactation decisions belong on the herb or product page where intake is actually decided, not on a molecule page — and for curine there is no human intake to decide about.

What is not known. Genotoxicity, carcinogenicity, repeat-dose toxicology beyond seven days, and any human safety assessment have not been performed for this compound.

Dosage

There is no human dose for curine, and no basis for one. It is not a supplement, not a drug, and not sold as an isolate for consumption. The figures below are the doses and concentrations studied in research, listed so the numbers here can be read in proportion — particularly the three-orders-of-magnitude gap between the effective dose and the paralytic one.

These are doses studied in research animals and cell cultures. They are not a personal recommendation, and none of them has ever been tested in a person.

References

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