Papaverine

Papaverine at a Glance

Papaverine is the odd molecule out in opium. It shares a plant and a biosynthetic origin with morphine and codeine but not a receptor: it is a 1-benzylisoquinoline, not a morphinan, it has no opioid activity, and it is neither analgesic nor narcotic. What it does is inhibit phosphodiesterase, raising intracellular cyclic AMP and cyclic GMP and relaxing smooth muscle — in blood vessels, in the gut, and most usefully in the erectile tissue of the penis ^{9Reference 9Ferrari M · 1974ReviewEffects of papaverine on smooth muscle and their mechanisms — reviewView study →}.

The striking thing about its clinical history is the route. Every established human use of papaverine is an injection, and each one is delivered into the tissue that is meant to respond: intracavernosal for erectile dysfunction ^{1,3Reference 1Virag R et al. · 1984Clinical trialIntracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure — clinical studyView study →Reference 3Belew D et al. · 2015ReviewIntracavernosal Injection for the Diagnosis, Evaluation, and Treatment of Erectile Dysfunction: A Review — reviewView study →}, intra-arterial for cerebral vasospasm after subarachnoid haemorrhage ^{6Reference 6Polin RS et al. · 1998ObservationalIntra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm — matched-cohort analysisView study →}, intracoronary to force maximal coronary blood flow during a diagnostic pressure measurement ^{5Reference 5van der Voort PH et al. · 1996Clinical trialComparison of intravenous adenosine to intracoronary papaverine for calculation of pressure-derived fractional flow reserve — clinical studyView study →}. That is not an accident of drug development. Oral papaverine reaches the bloodstream at an average of 28% of the injected dose, with an individual range of 5% to 99% ^{8Reference 8Berg G et al. · 1988Clinical trialVariable bioavailability of papaverine — human volunteersView study →}.

It has since acquired a second life that has nothing to do with medicine cabinets. It was the only extensively profiled pharmacological tool for phosphodiesterase 10A, the striatal enzyme behind a decade of schizophrenia drug discovery ^{10,11Reference 10Schmidt CJ et al. · 2008AnimalPreclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia — animal modelView study →Reference 11Hsu YT et al. · 2011In vitroThe PDE10A inhibitor, papaverine, differentially activates ERK in male and female rat striatal slices — in vitroView study →}, and it turned out to inhibit mitochondrial complex I, which is now being engineered into radiosensitisers for hypoxic tumours ^{13,14Reference 13Benej M et al. · 2018AnimalPapaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism — animal modelView study →Reference 14Haines BJ et al. · 2025In vitroDevelopment of Selective and Soluble Mitochondrial Complex 1 Inhibitors Derived from Papaverine for Radiosensitization of Cancer — in vitroView study →}.

Every Human Use Is an Injection

Papaverine’s pharmacology is not in dispute; its delivery is. Three distinct clinical uses developed independently, and all three are needles.

Into the penis. In 1982 Ronald Virag reported that intracavernosal papaverine produced erections, and the 1984 write-up established the pattern: 80 mg injected into the corpora produced erections within 10 minutes lasting one to four hours in potent volunteers and in men with psychogenic impotence, with weaker and shorter responses where there was arterial or venous disease; a pilot series of 63 men with angiogenic impotence reported significant improvement in 66% at a mean one-year follow-up ^{1Reference 1Virag R et al. · 1984Clinical trialIntracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure — clinical studyView study →}. Intracavernosal injection remains a guideline-recommended second-line therapy for erectile dysfunction — displaced to second line, not abolished, by the approval of oral PDE5 inhibitors in 1998 ^{3,4Reference 3Belew D et al. · 2015ReviewIntracavernosal Injection for the Diagnosis, Evaluation, and Treatment of Erectile Dysfunction: A Review — reviewView study →Reference 4Elena BW et al. · 2023ReviewCurrent status of intracavernosal injection therapy in erectile dysfunction — reviewView study →}.

Into a cerebral artery. Intra-arterial papaverine was adopted at some centres as standard management for symptomatic cerebral vasospasm after subarachnoid haemorrhage, on the strength of encouraging case series. When 31 patients who received it were matched against similar patients from the same trial cohort managed medically, there was no difference in three-month Glasgow Outcome Scale scores — 58% favourable outcomes in the controls versus 45% in the papaverine group ^{6Reference 6Polin RS et al. · 1998ObservationalIntra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm — matched-cohort analysisView study →}. The angiographic vessel opens; the patient does not do better.

Into a coronary artery. Intracoronary papaverine, at 12 mg into the left coronary artery or 10 mg into the right, has been described as the gold standard for inducing maximal coronary hyperaemia — the state required to measure fractional flow reserve across a stenosis. Its limitations are that the effect is too short-lived for steady-state pressure recording, and that it prolongs the QT interval, which is why intravenous adenosine displaced it for routine use ^{5Reference 5van der Voort PH et al. · 1996Clinical trialComparison of intravenous adenosine to intracoronary papaverine for calculation of pressure-derived fractional flow reserve — clinical studyView study →}.

And nothing oral. Papaverine was sold as an oral vasodilator for decades. A crossover study in nine healthy men and seven patients, comparing 80 mg intravenous with 80 mg oral, found mean bioavailability of 28% with a range of 5% to 99% — reproducible within an individual but wildly different between individuals, which the authors concluded was an unacceptable variation for an oral tablet ^{8Reference 8Berg G et al. · 1988Clinical trialVariable bioavailability of papaverine — human volunteersView study →}. A drug whose plasma level after a standard dose can differ twentyfold between two people cannot be titrated by mouth.

The implication for a poppy preparation is straightforward. Papaverine is a minor alkaloid in a latex dominated by morphinans ^{15Reference 15Frick S et al. · 2005Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivarsView study →}, the oral route is unreliable even with a measured pure dose, and none of the three routes that work is achievable outside a clinical setting.

What It's Used For

The evidence splits by route and by outcome type. Where papaverine is injected into the target tissue it does what it is supposed to do; where the endpoint is a clinical outcome rather than a vessel diameter, the picture is weaker.

Evidence by IndicationStrength of support · Beta

01Erectile Dysfunction (Intracavernosal)Promising54%45- and 63-patient original series plus a 160-man/13,030-injection clinic cohort; guideline second-line therapy ^{1,2,3,4Reference 1Virag R et al. · 1984Clinical trialIntracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure — clinical studyView study →Reference 2Armstrong DK et al. · 1993Clinical trialIntracavernosal papaverine and phentolamine for the medical management of erectile dysfunction in a genitourinary clinic — in patientsView study →Reference 3Belew D et al. · 2015ReviewIntracavernosal Injection for the Diagnosis, Evaluation, and Treatment of Erectile Dysfunction: A Review — reviewView study →Reference 4Elena BW et al. · 2023ReviewCurrent status of intracavernosal injection therapy in erectile dysfunction — reviewView study →}

02Coronary Hyperaemia (Intracoronary)Promising50%Long-standing reference agent for maximal hyperaemia in fractional-flow-reserve measurement; displaced by adenosine on duration and QT ^{5Reference 5van der Voort PH et al. · 1996Clinical trialComparison of intravenous adenosine to intracoronary papaverine for calculation of pressure-derived fractional flow reserve — clinical studyView study →}

03Cerebral Vasospasm (Intra-Arterial)Shaky22%Angiographic effect real; matched comparison found no outcome benefit (45% vs 58% favourable) ^{6Reference 6Polin RS et al. · 1998ObservationalIntra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm — matched-cohort analysisView study →}

04Tumour Radiosensitisation (Preclinical)Shaky16%Complex I inhibition raises tumour oxygenation and radiation response in models; derivatives in development, no human data ^{13,14Reference 13Benej M et al. · 2018AnimalPapaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism — animal modelView study →Reference 14Haines BJ et al. · 2025In vitroDevelopment of Selective and Soluble Mitochondrial Complex 1 Inhibitors Derived from Papaverine for Radiosensitization of Cancer — in vitroView study →}

05Oral Use And Poppy PreparationsShaky0%Oral bioavailability 28% mean, 5–99% range — judged unacceptable; no controlled evidence for any plant preparation ^{8,15Reference 8Berg G et al. · 1988Clinical trialVariable bioavailability of papaverine — human volunteersView study →Reference 15Frick S et al. · 2005Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivarsView study →}

Mechanisms

Papaverine’s problem as a drug and its usefulness as a research reagent have the same cause: it hits several unrelated targets at similar concentrations, so any effect it produces has more than one candidate explanation ^{10,13Reference 10Schmidt CJ et al. · 2008AnimalPreclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia — animal modelView study →Reference 13Benej M et al. · 2018AnimalPapaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism — animal modelView study →}.

Pharmacokinetics

The pharmacokinetics are the whole clinical story. After intravenous dosing, half-life ranged from 1.2 to 6.6 hours (mean 3.0), apparent volume of distribution averaged 3.1 L/kg and total plasma clearance 836 mL/min ^{8Reference 8Berg G et al. · 1988Clinical trialVariable bioavailability of papaverine — human volunteersView study →}. Oral bioavailability from an 80 mg tablet averaged 28%, spanning 5% to 99% across individuals — consistent within a person on repeat dosing, which points to fixed individual differences in first-pass handling rather than erratic absorption ^{8Reference 8Berg G et al. · 1988Clinical trialVariable bioavailability of papaverine — human volunteersView study →}. Injected directly into the tissue meant to respond, none of that matters; taken by mouth, all of it does.

Papaverine’s short systemic exposure was also the specific limitation flagged when it was used as the pharmacological probe for PDE10A: relatively poor potency, poor selectivity, and a very short exposure half-life after systemic administration ^{10Reference 10Schmidt CJ et al. · 2008AnimalPreclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia — animal modelView study →}.

Clinical Trials

Papaverine’s clinical record is historical rather than active. The erectile-dysfunction series predate modern trial standards, the vasospasm evidence is a matched-cohort comparison, and the coronary use is a diagnostic technique rather than a therapy. The live development work is preclinical, on derivatives designed to keep the complex I inhibition and discard the rest.

Last checked: September 2026.

A Second Life as a Research Tool

Papaverine’s most active present-day role is not therapeutic. For most of the 2000s it was the only pharmacological tool for phosphodiesterase 10A that had been extensively profiled — the striatum-enriched enzyme that regulates cAMP and cGMP signalling in the medium spiny neurons of the basal ganglia, and the target of a substantial schizophrenia drug-discovery effort. Almost everything understood about PDE10A’s physiological role in that period was learned with papaverine, and the programme’s first task was to replace it, because its potency and selectivity were poor and its systemic exposure very short ^{10Reference 10Schmidt CJ et al. · 2008AnimalPreclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia — animal modelView study →}. Work on rat striatal slices using papaverine as the probe found it activated ERK in D1- and D2-responsive neurons, and — unexpectedly — did so in males but almost not at all in females, a sex difference the tool compound made visible ^{11Reference 11Hsu YT et al. · 2011In vitroThe PDE10A inhibitor, papaverine, differentially activates ERK in male and female rat striatal slices — in vitroView study →}. The same PDE10 inhibition, working through PKA signalling, produces anti-inflammatory and neuroprotective effects in mouse models of neuroinflammation and Parkinson’s disease ^{12Reference 12Lee YY et al. · 2019AnimalThe phosphodiesterase 10 inhibitor papaverine exerts anti-inflammatory and neuroprotective effects via the PKA signaling pathway in neuroinflammation and Parkinson’s disease mouse models — animal modelView study →}.

The complex I story runs the other way. There, papaverine’s phosphodiesterase activity and vasodilation are the unwanted part: the useful action is the reduction in mitochondrial oxygen consumption that raises tumour oxygenation before radiotherapy, and derivatives have been built specifically to keep that and discard the rest ^{13,14Reference 13Benej M et al. · 2018AnimalPapaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism — animal modelView study →Reference 14Haines BJ et al. · 2025In vitroDevelopment of Selective and Soluble Mitochondrial Complex 1 Inhibitors Derived from Papaverine for Radiosensitization of Cancer — in vitroView study →}.

Both lines describe the same molecule from opposite directions. It is promiscuous enough to be a useful starting point for several unrelated targets, and too promiscuous to be a good drug for any of them.

Isolate vs. Plant Studies

There is no plant-side literature at all for this molecule, and the reason is unusually concrete. All of papaverine’s human evidence used the purified isolate delivered by injection — into the corpora, a cerebral artery or a coronary artery ^{1,2,5,6Reference 1Virag R et al. · 1984Clinical trialIntracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure — clinical studyView study →Reference 2Armstrong DK et al. · 1993Clinical trialIntracavernosal papaverine and phentolamine for the medical management of erectile dysfunction in a genitourinary clinic — in patientsView study →Reference 5van der Voort PH et al. · 1996Clinical trialComparison of intravenous adenosine to intracoronary papaverine for calculation of pressure-derived fractional flow reserve — clinical studyView study →Reference 6Polin RS et al. · 1998ObservationalIntra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm — matched-cohort analysisView study →}. The one route a plant preparation could deliver is the oral one, and that route was measured and found to produce a twentyfold spread of plasma exposure between individuals even from a standardised 80 mg tablet ^{8Reference 8Berg G et al. · 1988Clinical trialVariable bioavailability of papaverine — human volunteersView study →}.

Papaverine is also present in the plant in quantities that vary with cultivar, in a latex where the morphinan alkaloids dominate ^{15Reference 15Frick S et al. · 2005Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivarsView study →}. Any attempt to obtain a pharmacological dose of papaverine from poppy material would deliver a substantially larger opioid dose first.

The isolate-versus-plant question therefore has an unusually clean answer here: the isolate is not merely better studied — it is the only form in which this molecule has ever done anything measurable in a person.

Prevalence in Nature

Papaverine occurs in the latex of the opium poppy (Papaver somniferum), which produces around a hundred distinct benzylisoquinoline alkaloids from a shared pathway ^{16Reference 16Beaudoin GA · 2014ReviewBenzylisoquinoline alkaloid biosynthesis in opium poppy — reviewView study →}. It is a minor member of that set by quantity: in the Tasmanian pharmaceutical cultivar C048-6-14-64, 91.2% of latex alkaloids are morphine, codeine and thebaine alone, and the balance is divided among the remaining classes ^{15Reference 15Frick S et al. · 2005Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivarsView study →}. Cultivar changes the picture substantially — the condiment cultivar “Marianne” shifts almost entirely to the phthalideisoquinolines narcotoline and noscapine, with morphinans down to 18.8% — so the amount of papaverine in a given poppy is a property of the variety rather than of the species ^{15Reference 15Frick S et al. · 2005Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivarsView study →}.

Its Role in Plants

Papaverine sits on a different branch of the same tree as morphine. All the poppy’s benzylisoquinoline alkaloids descend from L-tyrosine through (S)-reticuline, which is the branch point: one route leads to the morphinans (thebaine, codeine, morphine), another to the phthalideisoquinolines such as noscapine, and another to the 1-benzylisoquinolines, of which papaverine is the best known ^{16,17Reference 16Beaudoin GA · 2014ReviewBenzylisoquinoline alkaloid biosynthesis in opium poppy — reviewView study →Reference 17Agarwal P et al. · 2019Agarwal P, Pathak S, Kumar RS, et al. (2019). 3’O-Methyltransferase, Ps3’OMT, from opium poppy: involvement in papaverine biosynthesis. Plant Cell Rep. https://pubmed.ncbi.nlm.nih.gov/31190213/View study →}. That shared origin and divergent endpoint is why one plant produces molecules acting on opioid receptors, on tubulin and on phosphodiesterases with no common pharmacology between them.

The final steps to papaverine are still contested. Two routes have been proposed — one running through N-desmethylated intermediates and one through N-methylated ones — and several steps in both lack characterised enzymes. A 3’-O-methyltransferase, Ps3’OMT, has been functionally linked to the pathway using a combination of computational, in-vitro and in-planta assays, but the route as a whole remains unsettled ^{17Reference 17Agarwal P et al. · 2019Agarwal P, Pathak S, Kumar RS, et al. (2019). 3’O-Methyltransferase, Ps3’OMT, from opium poppy: involvement in papaverine biosynthesis. Plant Cell Rep. https://pubmed.ncbi.nlm.nih.gov/31190213/View study →}.

Discovery & Synthesis

Papaverine was isolated from opium and named by Georg Merck in 1848, who reported it as a new organic base in opium — sixteen years after codeine and four decades after morphine, and named for the poppy genus rather than for any effect ^{18Reference 18Merck G · 1848Vorläufige Notiz über eine neue organische Base im OpiumView study →}.

Its first total synthesis was completed by Amé Pictet and Anton Gams in 1909 ^{19Reference 19Pictet A · 1909Synthese des PapaverinsView study →}. The route mattered beyond the molecule: the cyclodehydration step they developed became the Pictet–Gams isoquinoline synthesis, a named reaction still used to build isoquinoline ring systems.

Manufacture today is synthetic. Papaverine is not extracted at scale, because the plant supplies it as a minor component of a latex grown and licensed for its morphinan content; total synthesis from simple benzylisoquinoline precursors is the practical route. That independence from the poppy is a genuine difference from morphine and codeine, whose supply remains agricultural.

Patents: not yet researched.

Toxicity & Safety

Papaverine is not an opioid, and its safety profile has nothing in common with morphine’s — no respiratory depression, no dependence, no overdose antidote required. What it has instead are the hazards of a potent vasodilator given by injection.

Safety at a Glance

⚠️ Moderate toxicityDrug interactions

• No opioid activity. No analgesia, no euphoria, no respiratory depression and no dependence liability.
• Priapism is the characteristic complication of intracavernosal use — 22 episodes among 160 men in one clinic cohort, with corporeal fibrosis in one — and a prolonged erection is a urological emergency.
• QT prolongation. Intracoronary papaverine prolongs the QT interval and has caused torsade de pointes progressing to ventricular fibrillation.
• Hypotension and flushing follow predictably from systemic vasodilation.
• Oral dosing is not controllable. Bioavailability ranged from 5% to 99% between individuals in a controlled study, so an oral dose cannot be relied on to produce any particular exposure.

Full Safety & Interactions Detail

Priapism and injection-site complications. The dominant adverse effect of intracavernosal use, and the reason the therapy requires training and a dose established under supervision. In a cohort of 160 men given 13,030 papaverine-and-phentolamine injections, 16 patients experienced 22 episodes of priapism and one developed corporeal fibrosis ^{2Reference 2Armstrong DK et al. · 1993Clinical trialIntracavernosal papaverine and phentolamine for the medical management of erectile dysfunction in a genitourinary clinic — in patientsView study →}. Prolonged erection is time-critical: untreated low-flow priapism causes ischaemic damage to the cavernosal tissue and permanent erectile dysfunction. Repeated injection also carries a fibrosis risk over time, which is one reason intracavernosal therapy sits behind oral agents in current guidelines ^{3,4Reference 3Belew D et al. · 2015ReviewIntracavernosal Injection for the Diagnosis, Evaluation, and Treatment of Erectile Dysfunction: A Review — reviewView study →Reference 4Elena BW et al. · 2023ReviewCurrent status of intracavernosal injection therapy in erectile dysfunction — reviewView study →}.

Cardiac repolarisation. Papaverine prolongs the QT interval, a recognised limitation of its intracoronary use ^{5Reference 5van der Voort PH et al. · 1996Clinical trialComparison of intravenous adenosine to intracoronary papaverine for calculation of pressure-derived fractional flow reserve — clinical studyView study →}. In a documented case, a woman undergoing coronary flow reserve evaluation with intracoronary papaverine developed excessive QTU prolongation and torsade de pointes progressing to ventricular fibrillation; she had had drug-induced QT prolongation ten months earlier, which the authors identify as a risk factor ^{7Reference 7Goto M et al. · 2014Case reportPapaverine-induced QT interval prolongation and ventricular fibrillation in a patient with a history of drug-induced QT prolongation — case reportView study →}. Caution is warranted with any prior QT prolongation or concurrent QT-prolonging drug.

Systemic vasodilation. Flushing, hypotension and dizziness follow from the mechanism and are dose-related. Additive hypotension is expected with other vasodilators and antihypertensives, and the interaction with oral PDE5 inhibitors deserves specific mention: both raise cyclic nucleotide levels in the same tissue, and combining them is a clinical decision rather than a self-directed one ^{3,4Reference 3Belew D et al. · 2015ReviewIntracavernosal Injection for the Diagnosis, Evaluation, and Treatment of Erectile Dysfunction: A Review — reviewView study →Reference 4Elena BW et al. · 2023ReviewCurrent status of intracavernosal injection therapy in erectile dysfunction — reviewView study →}.

Unreliable oral exposure. The bioavailability finding is a safety point as much as an efficacy one. An individual at the top of the 5–99% range receives roughly three-and-a-half times the systemic exposure of an average person from the same tablet ^{8Reference 8Berg G et al. · 1988Clinical trialVariable bioavailability of papaverine — human volunteersView study →}.

No opioid liability. Papaverine is not a controlled narcotic and produces none of the opioid effects associated with its plant of origin ^{9,16Reference 9Ferrari M · 1974ReviewEffects of papaverine on smooth muscle and their mechanisms — reviewView study →Reference 16Beaudoin GA · 2014ReviewBenzylisoquinoline alkaloid biosynthesis in opium poppy — reviewView study →}. Its inclusion in the same latex as morphine is a fact of botany, not of pharmacology.

What is not known. No dedicated reproductive-toxicity dataset for isolated papaverine was identified in this pass, and its interaction profile has not been systematically characterised beyond the pharmacodynamic ones above.

Dosage

There is no oral or herbal dose. The figures below are the injected doses used in the studies cited, recorded as research figures.

Intracavernosal dosing in practice is established individually under supervision, because the dose that produces a usable erection in one man produces priapism in another — which is the same inter-individual variability the oral pharmacokinetics show, expressed at the target tissue ^{2,8Reference 2Armstrong DK et al. · 1993Clinical trialIntracavernosal papaverine and phentolamine for the medical management of erectile dysfunction in a genitourinary clinic — in patientsView study →Reference 8Berg G et al. · 1988Clinical trialVariable bioavailability of papaverine — human volunteersView study →}.

These are doses recorded in research, not a personal recommendation, and none of them describes anything that can be taken by mouth or obtained from a plant.

References

1. Virag R, Frydman D, Legman M, et al. (1984). Intracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure — clinical study. Angiology. https://pubmed.ncbi.nlm.nih.gov/6696289/
2. Armstrong DK, Convery A, Dinsmore WW (1993). Intracavernosal papaverine and phentolamine for the medical management of erectile dysfunction in a genitourinary clinic — in patients. Int J STD AIDS. https://pubmed.ncbi.nlm.nih.gov/8399501/
3. Belew D, Klaassen Z, Lewis RW (2015). Intracavernosal Injection for the Diagnosis, Evaluation, and Treatment of Erectile Dysfunction: A Review — review. Sex Med Rev. https://pubmed.ncbi.nlm.nih.gov/27784568/
4. Elena BW, Zachary M, Haritha P, et al. (2023). Current status of intracavernosal injection therapy in erectile dysfunction — review. Expert Opin Pharmacother. https://pubmed.ncbi.nlm.nih.gov/37078428/
5. van der Voort PH, van Hagen E, Hendrix G, et al. (1996). Comparison of intravenous adenosine to intracoronary papaverine for calculation of pressure-derived fractional flow reserve — clinical study. Cathet Cardiovasc Diagn. https://pubmed.ncbi.nlm.nih.gov/8922309/
6. Polin RS, Hansen CA, German P, et al. (1998). Intra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm — matched-cohort analysis. Neurosurgery. https://pubmed.ncbi.nlm.nih.gov/9632183/
7. Goto M, Sato M, Kitazawa H, et al. (2014). Papaverine-induced QT interval prolongation and ventricular fibrillation in a patient with a history of drug-induced QT prolongation — case report. Intern Med. https://pubmed.ncbi.nlm.nih.gov/25088875/
8. Berg G, Jönsson KA, Hammar M, et al. (1988). Variable bioavailability of papaverine — human volunteers. Pharmacol Toxicol. https://pubmed.ncbi.nlm.nih.gov/3413033/
9. Ferrari M (1974). Effects of papaverine on smooth muscle and their mechanisms — review. Pharmacol Res Commun. https://pubmed.ncbi.nlm.nih.gov/4373766/
10. Schmidt CJ, Chapin DS, Cianfrogna J, et al. (2008). Preclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia — animal model. J Pharmacol Exp Ther. https://pubmed.ncbi.nlm.nih.gov/18287214/
11. Hsu YT, Liao G, Bi X, et al. (2011). The PDE10A inhibitor, papaverine, differentially activates ERK in male and female rat striatal slices — in vitro. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/21816164/
12. Lee YY, Park JS, Leem YH, et al. (2019). The phosphodiesterase 10 inhibitor papaverine exerts anti-inflammatory and neuroprotective effects via the PKA signaling pathway in neuroinflammation and Parkinson’s disease mouse models — animal model. J Neuroinflammation. https://pubmed.ncbi.nlm.nih.gov/31791357/
13. Benej M, Hong X, Vibhute S, et al. (2018). Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism — animal model. Proc Natl Acad Sci U S A. https://pubmed.ncbi.nlm.nih.gov/30201710/
14. Haines BJ, Kreamer M, Benej M, et al. (2025). Development of Selective and Soluble Mitochondrial Complex 1 Inhibitors Derived from Papaverine for Radiosensitization of Cancer — in vitro. J Med Chem. https://pubmed.ncbi.nlm.nih.gov/41110127/
15. Frick S, Kramell R, Schmidt J, et al. (2005). Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivars. J Nat Prod. https://pubmed.ncbi.nlm.nih.gov/15921406/
16. Beaudoin GA, Facchini PJ (2014). Benzylisoquinoline alkaloid biosynthesis in opium poppy — review. Planta. https://pubmed.ncbi.nlm.nih.gov/24671624/
17. Agarwal P, Pathak S, Kumar RS, et al. (2019). 3’O-Methyltransferase, Ps3’OMT, from opium poppy: involvement in papaverine biosynthesis. Plant Cell Rep. https://pubmed.ncbi.nlm.nih.gov/31190213/
18. Merck G (1848). Vorläufige Notiz über eine neue organische Base im Opium. Justus Liebigs Annalen der Chemie. https://doi.org/10.1002/jlac.18480660121
19. Pictet A, Gams A (1909). Synthese des Papaverins. Berichte der deutschen chemischen Gesellschaft. https://doi.org/10.1002/cber.19090420311

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