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| Pronunciation | /pəˈpævəriːn/ |
| Trade names | Pavabid, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682707 |
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| Routes of administration | By mouth,intravenous,intramuscular,rectal,intracavernosal |
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| Pharmacokinetic data | |
| Bioavailability | 80% |
| Protein binding | ~90% |
| Metabolism | Hepatic |
| Eliminationhalf-life | 1.5–2 hours |
| Excretion | Renal |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.000.361 |
| Chemical and physical data | |
| Formula | C20H21NO4 |
| Molar mass | 339.391 g·mol−1 |
| 3D model (JSmol) | |
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Papaverine (Latinpapaver, "poppy") is anopiumalkaloidantispasmodic drug, used primarily in the treatment of visceralspasms andvasospasms (especially those involving the intestines, heart, or brain), occasionally in the treatment oferectile dysfunction andacute mesenteric ischemia. While it is found in theopium poppy, papaverine differs in both structure and pharmacological action from the analgesicmorphine and its derivatives (such ascodeine).
In addition to opium, papaverine is purported to be present in high concentrations instar gooseberry.[1]
Papaverine was discovered in 1848 by Georg Merck (1825–1873).[2] Merck was a student of the German chemistsJustus von Liebig andAugust Hofmann, and he was the son ofEmanuel Merck (1794–1855), founder of theMerck corporation, a major German chemical and pharmaceutical company.[3]
Papaverine is anisoquinoline alkaloid and the early steps in its biosynthesis fromtyrosine are well established.[4][5] The final step is known to be catalysed by the enzymetetrahydroberberine oxidase, whichoxidises (S)-tetrahydropapaverine:[5][6]
As of 2024[update], it is unclear whether (S)-tetrahydropapaverine derives from(S)-reticuline or(S)-coclaurine: the difference is whether thepiperidine nitrogen atom ismethylated at any point during the biosynthetic sequence.[5]
Papaverine is approved to treat spasms of the gastrointestinal tract,bile ducts andureter and for use as acerebral andcoronaryvasodilator insubarachnoid hemorrhage (combined withballoon angioplasty)[7] andcoronary artery bypass surgery.[8] Papaverine may also be used as a smooth muscle relaxant inmicrosurgery where it is applied directly to blood vessels.
Papaverine is used as anerectile dysfunction drug, alone or sometimes in combination.[9][10] Papaverine, when injected in penile tissue, causes directsmooth muscle relaxation and consequent filling of thecorpus cavernosum with blood resulting inerection. Atopical gel is also available for ED treatment.[11]
It is also commonly used incryopreservation ofblood vessels along with the otherglycosaminoglycans and protein suspensions.[12][13] Functions as avasodilator during cryopreservation when used in conjunction withverapamil,phentolamine,nifedipine,tolazoline ornitroprusside.[14][15]
Papaverine is also being investigated as a topical growth factor intissue expansion with some success.[16]
Papaverine is used as anoff-labelprophylaxis (preventative) ofmigraine headaches.[17][18][19] It is not a first line drug such as a fewbeta blockers,calcium channel blockers,tricyclic antidepressants, and someanticonvulsants such asdivalproex, but rather when these first line drugs and secondary drugs such asSSRIs,angiotensin II receptor antagonists, etc. fail in the prophylaxis of migraines, have intolerable side effects or are contraindicated.
Papaverine is also present in combinations of opium alkaloid salts such aspapaveretum (Omnopon,Pantopon) and others, along withmorphine,codeine, and in some casesnoscapine and others in a percentage similar to that in opium, or modified for a given application.
Papaverine is found as a contaminant in someheroin[20] and can be used by forensic laboratories in heroin profiling to identify its source.[21] The metabolites can also be found in the urine of heroin users, allowing street heroin to be distinguished from pharmaceuticaldiacetylmorphine.[22]
Thein vivo mechanism of action is not entirely clear, but an inhibition of theenzyme phosphodiesterase causing elevation of cyclic AMP and cyclic GMP[clarification needed] levels is significant. It may also altermitochondrialrespiration.
Papaverine has also been demonstrated to be a selectivephosphodiesterase inhibitor for thePDE10A subtype found mainly in thestriatum of the brain. When administered chronically to mice, it produced motor and cognitive deficits andincreased anxiety, but conversely may produce anantipsychotic effect,[23][24] although not all studies support this view.[25]
Frequent side effects of papaverine treatment include polymorphicventricular tachycardia, constipation, interference withsulphobromophthalein[citation needed] retention test (used to determine hepatic function), increasedtransaminase levels, increasedalkaline phosphatase levels,somnolence, andvertigo.
Rare side effects include flushing of the face,hyperhidrosis (excessive sweating),cutaneous eruption, arterialhypotension,tachycardia, loss of appetite,jaundice,eosinophilia,thrombopenia, mixedhepatitis, headache, allergic reaction, chronic active hepatitis, and paradoxical aggravation of cerebral vasospasm.[26]
Papaverine in the plantSauropus androgynus is linked tobronchiolitis obliterans.[27]
Papaverine is available in its salt form as thehydrochloride,codecarboxylate,adenylate, and teprosylate. It was also once available as a salt ofhydrobromide,camsylate, cromesilate,nicotinate, andphenylglycolate. The hydrochloride salt is available for intramuscular, intravenous, rectal and oral administration. The teprosylate is available in intravenous, intramuscular, and orally administered formulations. The codecarboxylate is available in oral form, only, as is the adenylate.
The codecarboxylate is sold under the name Albatran,[citation needed] the adenylate as Dicertan,[citation needed] and the hydrochloride salt is sold variously as Artegodan (Germany), Cardioverina (countries outside Europe and the United States), Dispamil (countries outside Europe and the United States), Opdensit (Germany), Panergon (Germany), Paverina Houde (Italy, Belgium), Pavacap (United States), Pavadyl (United States), Papaverine (Israel), Papaverin-Hamelin (Germany), Paveron (Germany), Spasmo-Nit (Germany), Cardiospan, Papaversan, Cepaverin, Cerespan, Drapavel, Forpaven, Papalease, Pavatest, Paverolan, Therapav (Canada[28]), Vasospan, Cerebid, Delapav, Dilaves, Durapav, Dynovas, Optenyl, Pameion, Papacon, Pavabid, Pavacen, Pavakey, Pavased, Pavnell, Alapav, Myobid, Vasal, Pamelon, Pavadel, Pavagen, Ro-Papav, Vaso-Pav, Papanerin-hcl, Qua bid, Papital T.R., Paptial T.R., Pap-Kaps-150.[citation needed] InHungary, papaverine andhomatropine methylbromide are used in mild drugs that help "flush" thebile.[29]
In addition to morphine, street heroin contains various alkaloids extracted from the opium poppy, Papaversomniferum, including codeine, thebaine, noscapine, and papaverine
-tetrahydropapaverine.svg)