Noscapine

Noscapine at a Glance

Noscapine is the poppy alkaloid that does none of the things opium is known for. It is a phthalideisoquinoline rather than a morphinan, it has no opioid-receptor activity, and it is neither analgesic, sedative nor addictive — which is why it has been sold across Europe and Japan for decades as an ordinary non-sedating cough suppressant ^{3Reference 3Mahmoudian M · 2009ReviewThe anti-cancer activity of noscapine: a review — reviewView study →}.

In 1998 a group at Emory reported that this benign cough medicine binds stoichiometrically to tubulin, arrests mammalian cells in metaphase and induces apoptosis — and did so with antitumour activity in mice, orally, at doses that appeared to spare normal tissue ^{1,2Reference 1Ye K et al. · 1998In vitroOpium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells — in vitro and animal modelView study →Reference 2Ke Y et al. · 2000AnimalNoscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses — animal modelView study →}. That single finding turned an old antitussive into a candidate anticancer drug and produced twenty-five years of preclinical work.

The follow-through is the honest part of the story. Two human oncology trials were registered; both were terminated, one for lack of clinical response, and neither published results ^{21,22Reference 21University of Southern California (2000– · 2000Clinical trialStudy of noscapine for patients with low grade non-Hodgkin’s lymphoma or chronic lymphocytic leukemia refractory to chemotherapy — phase 1/2 clinical trial; TERMINATED (“no funding”), enrolment 12, no results postedView study →Reference 22Cougar Biotechnology · 2007Clinical trialCougar Biotechnology, Inc. (2007–2010). A study of noscapine HCl (CB3304) in patients with relapsed or refractory multiple myeloma — phase 1 clinical trial; TERMINATED (“terminated early due to lack of clinical response”), enrolment 12, no results posted. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT00912899View study →}. A separate stroke programme produced a spectacular uncontrolled pilot, a null confirmatory trial, and a proposed mechanism that failed an independent bioassay ^{10,11,12Reference 10Mahmoudian M et al. · 2003Clinical trialA preliminary report on the application of noscapine in the treatment of stroke — uncontrolled pilot study in patientsView study →Reference 11Mahmoudian M et al. · 2015RCTA novel effect of Noscapine on patients with massive ischemic stroke: A pseudo-randomized clinical trialView study →Reference 12Bachelard H · 2022In vitroAre noscapine and raloxifene ligands of the bradykinin B(2) receptor? An assessment based on the human umbilical vein contractility assay — in vitroView study →}. And the tubulin binding that makes it interesting also makes it a reference aneugen in regulatory genotoxicity testing ^{14,15Reference 14Cheung JR et al. · 2015In vitroHistone markers identify the mode of action for compounds positive in the TK6 micronucleus assay — in vitroView study →Reference 15Igarashi M et al. · 2007AnimalOptimum conditions for detecting hepatic micronuclei caused by numerical chromosome aberration inducers in mice — animal modelView study →}.

A Tubulin Binder in a Cough Syrup

The central fact about noscapine is that two descriptions of it are both true and rarely stated together.

Description one: a mild antitussive. Noscapine has been used as an oral cough suppressant in many countries, valued precisely because it is not an opioid — no sedation, no analgesia, no dependence liability, and, in the animal and human record summarised at the time the anticancer work began, “very few toxic effects” ^{2,3Reference 2Ke Y et al. · 2000AnimalNoscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses — animal modelView study →Reference 3Mahmoudian M · 2009ReviewThe anti-cancer activity of noscapine: a review — reviewView study →}.

Description two: an antimitotic. Noscapine binds tubulin stoichiometrically, alters its conformation, affects microtubule assembly and arrests dividing cells in mitosis, after which they undergo apoptosis ^{1Reference 1Ye K et al. · 1998In vitroOpium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells — in vitro and animal modelView study →}. Its derivatives are described as reducing the dynamics of microtubules — the parameter taxanes and vinca alkaloids also disturb, but by driving polymer mass up or down, which is where much of their toxicity comes from ^{6Reference 6Li S et al. · 2012AnimalChemoprevention of familial adenomatous polyposis by bromo-noscapine (EM011) in the Apc(Min/+) mouse model — animal modelView study →}. That difference is the whole basis of the claim that noscapine is a gentler antimitotic.

Which is why the genotoxicology matters. A compound that interferes with the mitotic spindle produces daughter cells with the wrong number of chromosomes. Noscapine does exactly that, and the genetic-toxicology field uses it as a reference aneugen: it is one of the standard aneugenic comparators in the TK6 in-vitro micronucleus assay, characterised there by phosphorylated histone H3 and polyploidy markers rather than by the DNA-damage marker γH2AX ^{14Reference 14Cheung JR et al. · 2015In vitroHistone markers identify the mode of action for compounds positive in the TK6 micronucleus assay — in vitroView study →}. In vivo, single intravenous doses of 7.8–62.5 mg/kg induced micronucleated hepatocytes in partially hepatectomised mice — a model designed specifically to detect numerical chromosome aberration ^{15Reference 15Igarashi M et al. · 2007AnimalOptimum conditions for detecting hepatic micronuclei caused by numerical chromosome aberration inducers in mice — animal modelView study →}.

None of that makes noscapine acutely dangerous at the doses in a cough bottle, and it is not evidence of harm in people. But “binds tubulin, arrests mitosis, induces micronuclei by chromosome mis-segregation” and “gentle, non-toxic, over-the-counter” are descriptions of the same molecule, and the anticancer literature tends to quote only the second half.

The Oncology Programme That Reached Humans Twice

The preclinical case for noscapine is genuinely substantial, and it is worth setting out before the trials, because the gap between the two is the point.

What the animal work showed. Oral noscapine reduced the growth of murine lymphoid tumours and of human breast and bladder xenografts ^{1Reference 1Ye K et al. · 1998In vitroOpium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells — in vitro and animal modelView study →}, reduced lymphoma growth and extended survival in mice when given in the drinking water, with little or no toxicity to kidney, liver, heart, bone marrow, spleen or small intestine and no suppression of primary immune responses ^{2Reference 2Ke Y et al. · 2000AnimalNoscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses — animal modelView study →}. In a non-small-cell lung cancer xenograft it produced 49%, 65% and 86% reductions in tumour volume at 300, 450 and 550 mg/kg/day given orally for 24 days ^{4Reference 4Jackson T et al. · 2008AnimalAntitumor activity of noscapine in human non-small cell lung cancer xenograft model — animal modelView study →}. In triple-negative breast cancer it was strongly synergistic with doxorubicin — combination index values below 0.59 — with the combination cutting tumour volume by 82.9% against 39.4% for noscapine alone and 34.2% for doxorubicin alone, through suppression of NF-κB and anti-angiogenic signalling ^{5Reference 5Chougule MB et al. · 2011AnimalAntitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer — animal modelView study →}.

What happened in people. Two trials were registered and both were terminated:

• NCT00183950 — a Phase 1/2 study at the University of Southern California in low-grade non-Hodgkin’s lymphoma or chronic lymphocytic leukaemia refractory to chemotherapy, opened March 2000, enrolment 12. Terminated: “No funding.” ^{21Reference 21University of Southern California (2000– · 2000Clinical trialStudy of noscapine for patients with low grade non-Hodgkin’s lymphoma or chronic lymphocytic leukemia refractory to chemotherapy — phase 1/2 clinical trial; TERMINATED (“no funding”), enrolment 12, no results postedView study →}
• NCT00912899 — a Phase 1 dose-finding study of noscapine hydrochloride (CB3304) sponsored by Cougar Biotechnology in relapsed or refractory multiple myeloma, opened December 2007, enrolment 12. Terminated early “due to lack of clinical response.” ^{22Reference 22Cougar Biotechnology · 2007Clinical trialCougar Biotechnology, Inc. (2007–2010). A study of noscapine HCl (CB3304) in patients with relapsed or refractory multiple myeloma — phase 1 clinical trial; TERMINATED (“terminated early due to lack of clinical response”), enrolment 12, no results posted. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT00912899View study →}

Neither has published results.

The arithmetic that sits underneath. The xenograft results were obtained at 150–550 mg/kg/day ^{4,5Reference 4Jackson T et al. · 2008AnimalAntitumor activity of noscapine in human non-small cell lung cancer xenograft model — animal modelView study →Reference 5Chougule MB et al. · 2011AnimalAntitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer — animal modelView study →}. The doses noscapine has actually been given at in humans are the antitussive ones — 30 mg in the controlled cough comparison, 150 mg in the human pharmacokinetic study ^{8,9Reference 8Dahlström B et al. · 1982Pharmacokinetic properties of noscapine — pharmacokinetic study in healthy volunteersView study →Reference 9Empey DW et al. · 1979RCTComparison of the antitussive effects of codeine phosphate 20 mg, dextromethorphan 30 mg and noscapine 30 mg using citric acid-induced cough in normal subjects — placebo-controlled crossover studyView study →} — which is under 3 mg/kg for an adult. Oral bioavailability in those humans was 30%, with a 3.6-fold variation between individuals ^{8Reference 8Dahlström B et al. · 1982Pharmacokinetic properties of noscapine — pharmacokinetic study in healthy volunteersView study →}. The in-vitro IC50 against the lung and breast lines runs at 34.7 µM and 36–43 µM ^{4,5Reference 4Jackson T et al. · 2008AnimalAntitumor activity of noscapine in human non-small cell lung cancer xenograft model — animal modelView study →Reference 5Chougule MB et al. · 2011AnimalAntitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer — animal modelView study →}. Interspecies dose scaling closes some of that gap; it does not close all of it, and the terminated myeloma study is the only direct evidence of what happened when someone tried.

And the field’s own response was to leave the molecule behind. The active development line is not noscapine but noscapinoids — synthetic derivatives such as bromo-noscapine (EM011), designed for greater potency, which reduced both the number of new intestinal polyps (to 35% of untreated) and their mean size (to 42%) in the Apc^Min/+ mouse model of familial adenomatous polyposis ^{6Reference 6Li S et al. · 2012AnimalChemoprevention of familial adenomatous polyposis by bromo-noscapine (EM011) in the Apc(Min/+) mouse model — animal modelView study →}.

The Stroke Result That Did Not Replicate

Noscapine’s second clinical career rests on a claim that it antagonises the bradykinin B2 receptor, and therefore might limit the brain injury that bradykinin contributes to after ischaemic stroke. It ran through three stages, in a direction worth following.

The pilot (2003). Ten patients with acute ischaemic stroke were given oral noscapine and compared with ten who were not. Mortality was reported as 20% with noscapine against 80% in the control group, with improved clinical prognosis and no specific side effects ^{10Reference 10Mahmoudian M et al. · 2003Clinical trialA preliminary report on the application of noscapine in the treatment of stroke — uncontrolled pilot study in patientsView study →}. Allocation was not randomised and the groups were not blinded — and an 80% control mortality in acute ischaemic stroke is itself a signal that the two groups were not comparable.

The confirmatory trial (2015). The same group ran a larger pseudo-randomised study in massive middle-cerebral-artery stroke, allocating patients by their turn of arrival in the emergency department, with controls receiving supportive treatment only. At one month, 16 deaths in the control group against 11 in the noscapine group, P = 0.193, and no significant difference on either the modified Rankin scale or the Barthel index ^{11Reference 11Mahmoudian M et al. · 2015RCTA novel effect of Noscapine on patients with massive ischemic stroke: A pseudo-randomized clinical trialView study →}. The authors describe the 16% relative mortality reduction as “clinically remarkable” and call for larger studies. Read as written, it is a null result in a study that was not randomised, not placebo-controlled, and testing a hypothesis its own pilot had put at a fourfold mortality difference.

The mechanism (2022). An independent group tested the underlying premise directly, using the isolated human umbilical vein — an established contractile bioassay for bradykinin B2 ligands — against the reference peptide antagonist icatibant. Noscapine at 2.5 µM did not behave as a B2 receptor antagonist, at a concentration vastly exceeding an effective concentration of icatibant, and had no direct contractile effect. The authors suggest that the previously reported B2 inhibition may have been indirect physiological antagonism rather than receptor binding, and note that noscapine is better characterised as a putative sigma-receptor agonist ^{12Reference 12Bachelard H · 2022In vitroAre noscapine and raloxifene ligands of the bradykinin B(2) receptor? An assessment based on the human umbilical vein contractility assay — in vitroView study →}.

So the sequence runs: an implausibly large uncontrolled result, a null confirmatory study, and a mechanism that does not reproduce in an assay designed for it. All three are honest to publish; only the first is usually quoted.

What It's Used For

Noscapine has an unusual evidence shape — a long marketing history with almost no efficacy literature behind it, and a large preclinical literature with almost no clinical one in front of it.

Evidence by IndicationStrength of support · Beta

01Antimitotic Activity (Preclinical)Shaky32%Stoichiometric tubulin binding, metaphase arrest, oral xenograft regression, doxorubicin synergy — all animal and in vitro ^{1,2,4,5Reference 1Ye K et al. · 1998In vitroOpium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells — in vitro and animal modelView study →Reference 2Ke Y et al. · 2000AnimalNoscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses — animal modelView study →Reference 4Jackson T et al. · 2008AnimalAntitumor activity of noscapine in human non-small cell lung cancer xenograft model — animal modelView study →Reference 5Chougule MB et al. · 2011AnimalAntitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer — animal modelView study →}

02Cough SuppressionShaky22%Decades of licensed over-the-counter use in Europe and Japan; the one controlled comparison found showed no separation from placebo ^{3,9Reference 3Mahmoudian M · 2009ReviewThe anti-cancer activity of noscapine: a review — reviewView study →Reference 9Empey DW et al. · 1979RCTComparison of the antitussive effects of codeine phosphate 20 mg, dextromethorphan 30 mg and noscapine 30 mg using citric acid-induced cough in normal subjects — placebo-controlled crossover studyView study →}

03Ischaemic StrokeShaky8%Uncontrolled pilot, null pseudo-randomised follow-up, and a bradykinin mechanism that failed an independent bioassay ^{10,11,12Reference 10Mahmoudian M et al. · 2003Clinical trialA preliminary report on the application of noscapine in the treatment of stroke — uncontrolled pilot study in patientsView study →Reference 11Mahmoudian M et al. · 2015RCTA novel effect of Noscapine on patients with massive ischemic stroke: A pseudo-randomized clinical trialView study →Reference 12Bachelard H · 2022In vitroAre noscapine and raloxifene ligands of the bradykinin B(2) receptor? An assessment based on the human umbilical vein contractility assay — in vitroView study →}

04Anticancer Therapy (Human)Shaky0%Two registered trials, both terminated, no results published ^{21,22Reference 21University of Southern California (2000– · 2000Clinical trialStudy of noscapine for patients with low grade non-Hodgkin’s lymphoma or chronic lymphocytic leukemia refractory to chemotherapy — phase 1/2 clinical trial; TERMINATED (“no funding”), enrolment 12, no results postedView study →Reference 22Cougar Biotechnology · 2007Clinical trialCougar Biotechnology, Inc. (2007–2010). A study of noscapine HCl (CB3304) in patients with relapsed or refractory multiple myeloma — phase 1 clinical trial; TERMINATED (“terminated early due to lack of clinical response”), enrolment 12, no results posted. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT00912899View study →}

Mechanisms

Two of these rows are absences, and they carry as much weight as the positives — the opioid one explains why noscapine was ever an acceptable over-the-counter medicine, and the bradykinin one removes the rationale for the stroke work.

Pharmacokinetics

The human pharmacokinetics were established in 1982 in five healthy volunteers, in a randomised crossover of a 66 mg intravenous infusion against 150 mg oral tablets. Disposition after intravenous dosing was bi-exponential with an elimination half-life of 2.6 hours, total plasma clearance 22 mL/min/kg and volume of distribution 4.7 L/kg. Absolute oral bioavailability was 30%, with a 3.6-fold variation between individuals, and an ion-exchange-resin tablet gave no pharmacokinetic evidence of prolonged action ^{8Reference 8Dahlström B et al. · 1982Pharmacokinetic properties of noscapine — pharmacokinetic study in healthy volunteersView study →}.

In mice, mean oral bioavailability across 75–300 mg/kg was similar at 31.5%, with plasma concentrations after a 10 mg/kg intravenous bolus falling below detection by four hours ^{7Reference 7Aneja R et al. · 2007AnimalPreclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent — animal modelView study →}. Short half-life plus 30% bioavailability with a threefold interpersonal spread is a workable profile for a cough suppressant taken several times a day, and a poor one for an antimitotic that needs sustained exposure above a micromolar threshold.

Clinical Trials

The registry entries are the most informative part of this molecule’s clinical record, and what they record is two stops.

Last checked: September 2026.

Isolate vs. Plant Studies

Everything in this record is isolate work. The antitussive products are formulated noscapine or its hydrochloride; the pharmacokinetic study used measured intravenous and oral doses; the oncology work used pure compound at defined mg/kg; the trials used noscapine hydrochloride ^{1,4,7,8,22Reference 1Ye K et al. · 1998In vitroOpium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells — in vitro and animal modelView study →Reference 4Jackson T et al. · 2008AnimalAntitumor activity of noscapine in human non-small cell lung cancer xenograft model — animal modelView study →Reference 7Aneja R et al. · 2007AnimalPreclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent — animal modelView study →Reference 8Dahlström B et al. · 1982Pharmacokinetic properties of noscapine — pharmacokinetic study in healthy volunteersView study →Reference 22Cougar Biotechnology · 2007Clinical trialCougar Biotechnology, Inc. (2007–2010). A study of noscapine HCl (CB3304) in patients with relapsed or refractory multiple myeloma — phase 1 clinical trial; TERMINATED (“terminated early due to lack of clinical response”), enrolment 12, no results posted. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT00912899View study →}.

No poppy preparation has ever been studied as a source of noscapine, and the reasons are the same ones that apply across this plant’s alkaloids, with one addition specific to noscapine. Content varies enormously by cultivar — noscapine and narcotoline together are 80.5% of latex alkaloids in a condiment cultivar and a small fraction in a pharmaceutical one ^{18Reference 18Frick S et al. · 2005Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivarsView study →}. And in the varieties where noscapine is not dominant, any preparation delivering it delivers morphinans first.

The isolate-versus-plant question is therefore not close here. What is genuinely open is a different question: whether the isolate does anything useful in a person, which two terminated trials left unanswered ^{21,22Reference 21University of Southern California (2000– · 2000Clinical trialStudy of noscapine for patients with low grade non-Hodgkin’s lymphoma or chronic lymphocytic leukemia refractory to chemotherapy — phase 1/2 clinical trial; TERMINATED (“no funding”), enrolment 12, no results postedView study →Reference 22Cougar Biotechnology · 2007Clinical trialCougar Biotechnology, Inc. (2007–2010). A study of noscapine HCl (CB3304) in patients with relapsed or refractory multiple myeloma — phase 1 clinical trial; TERMINATED (“terminated early due to lack of clinical response”), enrolment 12, no results posted. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT00912899View study →}.

Prevalence in Nature

Noscapine occurs in the latex of the opium poppy (Papaver somniferum), one of roughly a hundred benzylisoquinoline alkaloids the plant produces ^{19,20Reference 19Vadhel A et al. · 2023ReviewOpium alkaloids, biosynthesis, pharmacology and association with cancer occurrence — reviewView study →Reference 20Beaudoin GA · 2014ReviewBenzylisoquinoline alkaloid biosynthesis in opium poppy — reviewView study →}. Its share of that mixture is a property of the variety rather than the species, and the range is wide. In the Tasmanian pharmaceutical cultivar C048-6-14-64, 91.2% of latex alkaloids are morphine, codeine and thebaine, leaving the phthalideisoquinolines a minor component; in the condiment cultivar “Marianne”, grown for seed, the picture inverts — morphinans fall to 18.8% and narcotoline and noscapine together account for 80.5% of latex alkaloids ^{18Reference 18Frick S et al. · 2005Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivarsView study →}. Dedicated high-noscapine breeding lines exist and were the material in which the biosynthetic genes were found ^{16Reference 16Winzer T et al. · 2012A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapineView study →}.

Its Role in Plants

Noscapine sits on the phthalideisoquinoline branch of benzylisoquinoline metabolism — the same (S)-reticuline branch point that leads elsewhere to the morphinans and to the 1-benzylisoquinolines such as papaverine ^{20Reference 20Beaudoin GA · 2014ReviewBenzylisoquinoline alkaloid biosynthesis in opium poppy — reviewView study →}.

The way the plant organises that branch is unusual enough to have made the molecule famous a second time. Transcriptomic analysis of a high-noscapine poppy variety found ten genes encoding five distinct enzyme classes expressed exclusively in that variety, and mapping plus bacterial-artificial-chromosome sequencing showed they are tightly linked in a single genomic cluster — one of the clearest examples of a complex gene cluster for plant alkaloid biosynthesis ^{16Reference 16Winzer T et al. · 2012A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapineView study →}. Silencing genes in the cluster caused pathway intermediates to accumulate, which is how the individual steps were assigned ^{16Reference 16Winzer T et al. · 2012A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapineView study →}.

That organisation is also what made the pathway portable. In 2016 the cluster was reconstituted in Saccharomyces cerevisiae, and a yeast strain expressing 16 heterologous plant enzymes was engineered to run the full 14-step route from the simple alkaloid norlaudanosoline to noscapine — along the way validating the secoberberine intermediates and identifying a narcotoline 4’-O-methyltransferase that appears to work as a heterodimer ^{17Reference 17Li Y · 2016Engineering biosynthesis of the anticancer alkaloid noscapine in yeastView study →}.

Discovery & Synthesis

Noscapine spent most of its history under a different name. It was known as narcotine through nineteenth- and twentieth-century opium chemistry, and was renamed because the old name asserts a property the molecule does not have — it is not narcotic, and the name kept implying otherwise. The alternative name methoxyhydrastine records its structural kinship to hydrastine, the phthalideisoquinoline of goldenseal.

Production remains agricultural. Noscapine is extracted from poppy varieties bred to accumulate it, rather than synthesised at scale — the elucidation of the gene cluster was explicitly motivated by the prospect of improving commercial production ^{16Reference 16Winzer T et al. · 2012A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapineView study →}. The 2016 yeast reconstitution is the plausible route to a manufactured supply and to pathway intermediates that the plant does not make accessible, but it is a laboratory achievement rather than a production process ^{17Reference 17Li Y · 2016Engineering biosynthesis of the anticancer alkaloid noscapine in yeastView study →}.

Patents: not yet researched.

Toxicity & Safety

Noscapine’s acute toxicity is genuinely low — that is why it has been an over-the-counter medicine for decades, and the animal work at tumour-suppressive doses found little or no organ damage and no suppression of immune responses ^{2Reference 2Ke Y et al. · 2000AnimalNoscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses — animal modelView study →}. The moderate flag here reflects two specific findings rather than any acute hazard: a documented interaction with warfarin, and the aneugenicity that follows from its mechanism.

Safety at a Glance

⚠️ Moderate toxicityBleeding risk

• Not an opioid. No sedation, no analgesia, no respiratory depression, no dependence liability.
• Low acute toxicity at antitussive doses, and no organ toxicity or immune suppression at tumour-suppressive doses in animals.
• Warfarin interaction. Noscapine has raised INR in anticoagulated patients — a documented, and potentially dangerous, over-the-counter drug interaction.
• It is a reference aneugen. The tubulin binding that underlies the anticancer interest also causes chromosome mis-segregation, and noscapine is used as a standard aneugenic comparator in regulatory genotoxicity assays.
• Oral exposure is variable. Bioavailability of about 30%, with a 3.6-fold spread between individuals.

Full Safety & Interactions Detail

Warfarin. The clinically important interaction, and one that matters precisely because noscapine is bought without a prescription. A series of four case reports documented raised international normalised ratio in patients on warfarin who took noscapine-containing cough preparations, and the interaction has been described in the literature as potentially dangerous ^{13Reference 13Scordo MG et al. · 2008Case reportWarfarin-noscapine interaction: a series of four case reports — case reportView study →}. Anyone on warfarin should treat a noscapine cough medicine as a drug interaction, not as an inert purchase.

Aneugenicity and genotoxicity. Noscapine is positive in the in-vitro micronucleus assay and is used by the genetic-toxicology field as a reference aneugen — a compound that produces micronuclei by causing whole-chromosome loss rather than by breaking DNA. In the TK6 assay it is characterised by induction of phosphorylated histone H3 and polyploidy, the aneugenicity markers, rather than by γH2AX, the clastogenicity marker ^{14Reference 14Cheung JR et al. · 2015In vitroHistone markers identify the mode of action for compounds positive in the TK6 micronucleus assay — in vitroView study →}. In vivo, single intravenous doses of 7.8–62.5 mg/kg induced micronucleated hepatocytes in partially hepatectomised mice, alongside binucleated and multinucleated cells, in a model built to detect numerical chromosome aberration ^{15Reference 15Igarashi M et al. · 2007AnimalOptimum conditions for detecting hepatic micronuclei caused by numerical chromosome aberration inducers in mice — animal modelView study →}. This is a mechanistic consequence of binding tubulin, not an idiosyncratic contaminant effect, and it applies to the molecule at any dose that reaches an antimitotic concentration. It has not been shown to translate into a clinical risk at antitussive doses, and it has not been shown not to.

Antimitotic activity as a general caution. A compound that arrests dividing cells in mitosis acts preferentially on rapidly proliferating tissue. The animal work is reassuring on bone marrow and gut at the doses tested ^{2Reference 2Ke Y et al. · 2000AnimalNoscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses — animal modelView study →}, but the mechanism is the same one that makes cytotoxic chemotherapy hazardous, and the anticancer literature’s habit of describing noscapine as “non-toxic” describes an observed dose range, not a property of the molecule.

Reproductive note. No dedicated reproductive-toxicity dataset for noscapine was identified in this pass. That absence is worth stating plainly rather than reading as reassurance, because a tubulin-binding aneugen is exactly the pharmacological class for which such data would be wanted.

What is not known. Beyond the warfarin interaction, noscapine’s drug-interaction profile has not been systematically characterised in the sources reviewed here; no CYP-mediated interaction burden is described either way.

Dosage

The doses recorded below are the ones used in the studies cited. They are not a recommendation, and the two groups of figures are not on the same scale.

The distance between rows two and three is the practical summary of this molecule. An adult taking the largest dose noscapine has been given in a human study receives well under 3 mg/kg; the antitumour work runs at a hundred times that or more, before accounting for a 30% oral bioavailability that varies threefold between people ^{4,5,8Reference 4Jackson T et al. · 2008AnimalAntitumor activity of noscapine in human non-small cell lung cancer xenograft model — animal modelView study →Reference 5Chougule MB et al. · 2011AnimalAntitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer — animal modelView study →Reference 8Dahlström B et al. · 1982Pharmacokinetic properties of noscapine — pharmacokinetic study in healthy volunteersView study →}.

No dose of any kind can be obtained from poppy material, whose noscapine content ranges from a minor share of latex alkaloids to the large majority depending on the variety ^{18Reference 18Frick S et al. · 2005Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivarsView study →}.

These are doses recorded in research, not a personal recommendation.

References

1. Ye K, Ke Y, Keshava N, et al. (1998). Opium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells — in vitro and animal model. Proc Natl Acad Sci U S A. https://pubmed.ncbi.nlm.nih.gov/9465062/
2. Ke Y, Ye K, Grossniklaus HE, et al. (2000). Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses — animal model. Cancer Immunol Immunother. https://pubmed.ncbi.nlm.nih.gov/10941904/
3. Mahmoudian M, Rahimi-Moghaddam P (2009). The anti-cancer activity of noscapine: a review — review. Recent Pat Anticancer Drug Discov. https://pubmed.ncbi.nlm.nih.gov/19149691/
4. Jackson T, Chougule MB, Ichite N, et al. (2008). Antitumor activity of noscapine in human non-small cell lung cancer xenograft model — animal model. Cancer Chemother Pharmacol. https://pubmed.ncbi.nlm.nih.gov/18338172/
5. Chougule MB, Patel AR, Jackson T, et al. (2011). Antitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer — animal model. PLoS One. https://pubmed.ncbi.nlm.nih.gov/21423660/
6. Li S, Ghaleb AM, He J, et al. (2012). Chemoprevention of familial adenomatous polyposis by bromo-noscapine (EM011) in the Apc(Min/+) mouse model — animal model. Int J Cancer. https://pubmed.ncbi.nlm.nih.gov/22052467/
7. Aneja R, Dhiman N, Idnani J, et al. (2007). Preclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent — animal model. Cancer Chemother Pharmacol. https://pubmed.ncbi.nlm.nih.gov/17285314/
8. Dahlström B, Mellstrand T, Löfdahl CG, et al. (1982). Pharmacokinetic properties of noscapine — pharmacokinetic study in healthy volunteers. Eur J Clin Pharmacol. https://pubmed.ncbi.nlm.nih.gov/7128665/
9. Empey DW, Laitinen LA, Young GA, et al. (1979). Comparison of the antitussive effects of codeine phosphate 20 mg, dextromethorphan 30 mg and noscapine 30 mg using citric acid-induced cough in normal subjects — placebo-controlled crossover study. Eur J Clin Pharmacol. https://pubmed.ncbi.nlm.nih.gov/527635/
10. Mahmoudian M, Mehrpour M, Benaissa F, et al. (2003). A preliminary report on the application of noscapine in the treatment of stroke — uncontrolled pilot study in patients. Eur J Clin Pharmacol. https://pubmed.ncbi.nlm.nih.gov/14517705/
11. Mahmoudian M, Rezvani M, Rohani M, et al. (2015). A novel effect of Noscapine on patients with massive ischemic stroke: A pseudo-randomized clinical trial. Iran J Neurol. https://pubmed.ncbi.nlm.nih.gov/25874051/
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