Papaverine

Papaverine
Papaverine
Systematic (IUPAC) name
1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline
Clinical data
Trade names Pavabid
AHFS/Drugs.com monograph
MedlinePlus a682707
Pregnancy cat. USA: C[4]
Legal status  ?
Routes Oral, intravenous, intramuscular, rectal,[5] intracavernosal
Pharmacokinetic data
Bioavailability 80%[3]
Protein binding ~90%
Metabolism Hepatic[3]
Half-life 1.5–2 hours[3]
Excretion Renal[3]
Identifiers
CAS number 58-74-2
61-25-6 (hydrochloride)
ATC code A03AD01 G04BE02
PubChem CID 4680
DrugBank APRD00628
ChemSpider 4518 YesY
UNII DAA13NKG2Q YesY
KEGG D07425 YesY
ChEMBL CHEMBL19224 YesY
Chemical data
Formula C20H21NO4 
Mol. mass 339.385 g/mol[1]
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

Papaverine (play /pəˈpævəriːn/)[1] is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasm, vasospasm (especially those involving the heart and the brain), and occasionally in the treatment of erectile dysfunction.[3] While it is found in the opium poppy, papaverine differs in both structure and pharmacological action from the analgesic (morphine-related) opium alkaloids (opioids).

Contents

Uses

Papaverine is approved to treat spasms of the gastrointestinal tract, bile ducts and ureter and for use as a cerebral and coronary vasodilator[3] in subarachnoid hemorrhage (combined with balloon angioplasty)[6] and coronary artery bypass surgery.[7] Papaverine may also be used as a smooth muscle relaxant in microsurgery where it is applied directly to blood vessels.

Papaverine is used as an erectile dysfunction drug, alone or sometimes in combination.[2][3] Papaverine, when injected in penile tissue causes direct smooth muscle relaxation and consequent filling of the corpus cavernosum with blood resulting in erection. A topical gel is also available for ED treatment.[4]

It is also commonly used in cryopreservation of blood vessels along with the other glycosaminoglycans and protein suspensions.[5][6] Functions as a vasodilator during cryopreservation when used in conjunction with verapamil, phentolamine, nifedipine, tolazoline or nitroprusside.[7][8]

Papaverine is also being investigated as a topical growth factor in tissue expansion with some success.[9]

Papaverine is used as an off label prophylaxis (preventative) of migraine headaches.[10][11][12] It is not a first line drug such as a few beta blockers, calcium channel blockers, tricyclic antidepressants, and some anticonvulsants such as divalproex, but rather when these first line drugs and secondary drugs such as SSRIs, 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 as papaveretum (Omnopon, Pantopon) and others, along with morphine, codeine, and in some cases noscapine and others in a percentage similar to that in opium, or modified for a given application.

Mechanism

The in vivo mechanism of action is not entirely clear, but an inhibition of the enzyme phosphodiesterase causing elevation of cyclic AMP levels is significant. It may also alter mitochondrial respiration.

Papaverine has also been demonstrated to be a selective phosphodiesterase inhibitor for the PDE10A subtype found mainly in the striatum of the brain. When administered chronically to mice, it produced motor and cognitive deficits and increased anxiety, but conversely may produce an antipsychotic effect.,[13][14] even though not all studies support this view.[15]

Side effects

Frequent side effects of papaverine treatment include polymorphic ventricular tachycardia, constipation, interference with sulphobromophthalein[8] retention test (used to determine hepatic function), increased transaminase levels, increased alkaline phosphatase levels, somnolence, and vertigo.[3]

Rare side effects include flushing of the face, hyperhidrosis (excessive sweating), cutaneous eruption, arterial hypotension, tachycardia, loss of appetite, jaundice, eosinophilia, thrombopenia, mixed hepatitis, headache, allergic reaction, chronic active hepatitis,[3] and paradoxical aggravation of cerebral vasospasm.[9]

Formulations and trade names

Papaverine is available as a conjugate of hydrochloride, codecarboxylate, adenylate, and teprosylate.[10] It was also once available as a salt of hydrobromide, camsylate, cromesilate, nicotinate, and phenylglycolate. The hydrochloride salt is available for intramuscular, intravenous, rectal and oral administration.[5] The teprosylate is available in intravenous, intramuscular, and orally administered formulations.[11] The codecarboxylate is available in oral form, only,[12] as is the adenylate.[13]

The codecarboxylate is sold under the name Albatran,[14] the adenylate as Dicertan,[15] 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),[5] Cardiospan, Papaversan, Cepaverin, Cerespan, Drapavel, Forpaven, Papalease, Pavatest, Paverolan, Therapav (France[16]), 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.[17]. In Hungary, papaverine and homatropine methylbromide are used in mild drugs that help "flush" the bile (e.g. Neo-Bilagit).

References

  1. ^ Papaverine - EverydayHealth.com
  2. ^ Desvaux, P (2005). "An overview of the management of erectile disorders". Presse medicale (Paris, France : 1983) 34 (13 Suppl): 5–7. PMID 16158020.  edit
  3. ^ Bella, A. J.; Brock, G. B. (2004). "Intracavernous Pharmacotherapy for Erectile Dysfunction". Endocrine 23 (2–3): 149–155. doi:10.1385/ENDO:23:2-3:149. PMID 15146094.  edit
  4. ^ Kim, E.; Elrashidy, R.; McVary, K. (1995). "Papaverine Topical Gel for Treatment of Erectile Dysfunction". The Journal of Urology 153 (2): 361. doi:10.1097/00005392-199502000-00019. PMID 7815584.  edit
  5. ^ Müller-Schweinitzer E, Ellis P (May 1992). "Sucrose promotes the functional activity of blood vessels after cryopreservation in DMSO-containing fetal calf serum". Naunyn Schmiedebergs Arch. Pharmacol. 345 (5): 594–7. PMID 1528275. 
  6. ^ Müller-Schweinitzer E, Hasse J, Swoboda L (1993). "Cryopreservation of human bronchi". J Asthma 30 (6): 451–7. doi:10.3109/02770909309056754. PMID 8244915. 
  7. ^ Brockbank KG (February 1994). "Effects of cryopreservation upon vein function in vivo". Cryobiology 31 (1): 71–81. doi:10.1006/cryo.1994.1009. PMID 8156802. http://linkinghub.elsevier.com/retrieve/pii/S0011-2240(84)71009-1. 
  8. ^ Giglia JS, Ollerenshaw JD, Dawson PE, Black KS, Abbott WM (November 2002). "Cryopreservation prevents arterial allograft dilation". Ann Vasc Surg 16 (6): 762–7. doi:10.1007/s10016-001-0072-1. PMID 12391500. 
  9. ^ Tang Y, Luan J, Zhang X (2004). "Accelerating tissue expansion by application of topical papaverine cream". Plast. Reconstr. Surg. 114 (5): 1166–9. doi:10.1097/01.PRS.0000135854.48570.76. PMID 15457029. 
  10. ^ Sillanpää, M; Koponen, M (1978). "Papaverine in the prophylaxis of migraine and other vascular headache in children". Acta paediatrica Scandinavica 67 (2): 209–12. doi:10.1111/j.1651-2227.1978.tb16304.x. PMID 343489.  edit
  11. ^ Vijayan, N. (1977). "Brief therapeutic report: papaverine prophylaxis of complicated migraine". Headache 17 (4): 159–162. doi:10.1111/j.1526-4610.1977.hed1704159.x. PMID 893088.  edit
  12. ^ Poser, C. M. (1974). "Letter: Papaverine in prophylactic treatment of migraine". Lancet 1 (7869): 1290. doi:10.1016/S0140-6736(74)90045-2. PMID 4134173.  edit
  13. ^ Siuciak JA, Chapin DS, Harms JF, et al. (August 2006). "Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis". Neuropharmacology 51 (2): 386–96. doi:10.1016/j.neuropharm.2006.04.013. PMID 16780899. http://linkinghub.elsevier.com/retrieve/pii/S0028-3908(06)00106-7. 
  14. ^ Hebb AL, Robertson HA, Denovan-Wright EM (May 2008). "Phosphodiesterase 10A inhibition is associated with locomotor and cognitive deficits and increased anxiety in mice". Eur Neuropsychopharmacol 18 (5): 339–63. doi:10.1016/j.euroneuro.2007.08.002. PMID 17913473. http://linkinghub.elsevier.com/retrieve/pii/S0924-977X(07)00172-1. 
  15. ^ Weber M, Breier M, Ko D, Thangaraj N, Marzan DE, Swerdlow NR (May 2009). "Evaluating the antipsychotic profile of the preferential PDE10A inhibitor, papaverine". Psychopharmacology (Berl.) 203 (4): 723–35. doi:10.1007/s00213-008-1419-x. PMC 2748940. PMID 19066855. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2748940. 
  1. a b c "SID 544606 — PubChem Substance Summary". http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=544606. 
  2. a "Papaverine Material Safety Data Sheet". http://bulkpharm.mallinckrodt.com/_attachments/msds/PAPVN.htm. Retrieved 25 September 2005. 
  3. a b c d e f g h Unknown (2000). "PAPAVERINE". Molécule(s) de base: PAPAVERINE. Biam. http://www.biam2.org/www/Sub3015.html. Retrieved 25 September 2005.  (French)
  4. a Unknown (2004). "Who should not take papaverine?". papaverine Consumer Drug Information. Cerner Multum, Inc. http://www.drugs.com/MTM/papaverine.html. Retrieved 26 September 2005. 
  5. a b c Unknown (1999). "PAPAVERINE CHLORHYDRATE". Molécule(s) de base: PAPAVERINE. Biam. http://www.biam2.org/www/Sub65.html. Retrieved 25 September 2005.  (French)
  6. a Liu JK, Couldwell WT (2005). "Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage". Neurocrit Care 2 (2): 124–32. doi:10.1385/NCC:2:2:124. PMID 16159054. 
  7. a Takeuchi K, Sakamoto S, Nagayoshi Y, Nishizawa H, Matsubara J (November 2004). "Reactivity of the human internal thoracic artery to vasodilators in coronary artery bypass grafting". Eur J Cardiothorac Surg 26 (5): 956–9. doi:10.1016/j.ejcts.2004.07.047. PMID 15519189. http://linkinghub.elsevier.com/retrieve/pii/S1010-7940(04)00621-9. 
  8. a "SID 149219 — PubChem Substance Summary". http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=149219. 
  9. a Clyde BL, Firlik AD, Kaufmann AM, Spearman MP, Yonas H (April 1996). "Paradoxical aggravation of vasospasm with papaverine infusion following aneurysmal subarachnoid hemorrhage. Case report". J. Neurosurg. 84 (4): 690–5. doi:10.3171/jns.1996.84.4.0690. PMID 8613866. http://thejns.org/doi/abs/10.3171/jns.1996.84.4.0690?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov. 
  10. a "Molécule de base: PAPAVERINE". http://www.biam2.org/www/Gsu1575.html. Retrieved 26 September 2005.  Biam.
  11. a Unknown (1999). "PAPAVERINE TEPROSILATE". Molécule(s) de base: PAPAVERINE. Biam. http://www.biam2.org/www/Sub70.html. Retrieved 26 September 2005.  (French)
  12. a Unknown (1998). "PAPAVERINE CODECARBOXYLATE". Molécule(s) de base: PAPAVERINE. Biam. http://www.biam2.org/www/Sub1293.html. Retrieved 26 September 2005.  (French)
  13. a Unknown (1998). "PAPAVERINE ADENYLATE". Molécule(s) de base: PAPAVERINE. Biam. http://www.biam2.org/www/Sub1295.html. Retrieved 26 September 2005.  (French)
  14. a "SID 660773 — PubChem Substance Summary". http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=660773. 
  15. a "SID 660767 — PubChem Substance Summary". http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=660767. 
  16. a "THERAPAV (PRODUIT PUR) - Détail". http://www.reptox.csst.qc.ca/Produit.asp?no_produit=108688&nom=THERAPAV+(PRODUIT+PUR)&incr=0. Retrieved 26 September 2005.  CSST - Service du répertoire toxicologique. (French)
  17. a "SID 660767 — PubChem Substance Summary — Depositor-Supplied Synonyms: All". http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=40460&ncount=61#Synonyms. 
v · Opium components
Alkaloids

16-Hydroxythebaine • Berberine • Canadine • Codamine • Coptisine • Coreximine • Cycloartenol • Cycloartenone • Cyclolaudenol • Dehydroreticuline • Dihydrosanguinarine • Glaucine • Isoboldine • Isocorypalmine • Laudanidine • Magnoflorine • Narceinone • Norlaudanosoline • Norsanguinarine • Oripavine • Oxysanguinarine • Palaudine • Papaverrubine B (O-Methyl-Porphyroxine) • Papaverrubine C (Epiporphyroxine) • Reticuline • Salutaridine (Sinoacutine) • Sanguinarine • Scoulerine • Somniferine • Stepholidine
Morphine group
(Phenanthrenes. Includes opioids)

Codeine • Morphine • Narceine • Narcotoline • Neopine • Noscapine (Narcotine) • Perparin • Papaverrubine D (Porphyroxine) • Pseudocodeine • Pseudomorphine • Thebaine
Isoquinolines

Cotarnine • Eupaverine • Hydrocotarnine • Laudanosine • Laudanine • Papaverine • Papaveraldine • Xanthaline
Protopine group

α-Allocryptopine • α-Fagarine • Corycavamine • Corycavine • Cryptopine • Protopine
Tetrahydroprotoberberine group

Corydaline • Corybulbine • Isocorybulbine • Capaurine
Aporphine group

Dicentrine • Glaucine • Corytuberine • Cularine • Corydine • Isocorydine • Bulbocapnine
Phtalide-isoquinolines

Adulmine • Bicuculine • Bicucine • Corlumine
α-Naphthaphenanthridines

Chelidonine • β-Homochelidonoine • Chelerythrine • Sanguinarine
Other components
v · d · eDrugs for functional gastrointestinal disorders (A03)
Drugs for
functional bowel disorders
Tertiary
amino group
Quaternary ammonium
compounds
Benzilone • Mepenzolate • Pipenzolate • Glycopyrronium • Oxyphenonium • Penthienate • Methantheline • Propantheline • Otilonium bromide • Tridihexethyl • Isopropamide • Hexocyclium • Poldine • Bevonium • Diphemanil • Tiemonium iodide • Prifinium bromide • Timepidium bromide • Fenpiverinium
Papaverine • Drotaverine • Moxaverine
Other
Fenpiprane • Diisopromine • Chlorbenzoxamine • Pinaverium • Fenoverine • Idanpramine • Proxazole • Alverine • Trepibutone • Isometheptene • Caroverine • Phloroglucinol • Silicones • Trimethyldiphenylpropylamine
Belladonna and derivatives
(antimuscarinics)

tertiary amines: Atropine • Hyoscyamine

quaternary ammonium compounds: Scopolamine (Butylscopolamine, Methylscopolamine) • Methylatropine • Fentonium • Cimetropium bromide
Propulsives

M: DIG

anat(t, g, p)/phys/devp/enzy

noco/cong/tumr, sysi/epon

proc, drug(A2A/2B/3/4/5/6/7/14/16), blte
v · G04BE) and premature ejaculation
For erectile dysfunction
ABT-670 • ABT-724
Others
Apomorphine • Papaverine
For premature ejaculation
Oxytocin receptor antagonists
Epelsiban

M: ♂ MRS

anat/phys/devp

noco/cong/tumr, sysi/epon

proc, drug (G3B/4BE/4C)
v · d · ePhosphodiesterase inhibitors
PDE1
MMPX • SCH-51866 • Vinpocetine
PDE2
BAY 60-7550 • EHNA
PDE3
Amrinone • Anagrelide • Bucladesine • Cilostamide • Cilostazol • Enoximone • KMUP-1 • Milrinone • Quazinone • RPL-554 • Siguazodan • Trequinsin • Vesnarinone • Zardaverine
PDE4
Arofylline • Cilomilast • CP-80633 • Denbutylline • Drotaverine • Etazolate • Filaminast • Glaucine • HT-0712 • Ibudilast • ICI-63197 • Irsogladine • Luteolin • Mesembrine • Roflumilast • Rolipram • Ro20-1724 • RPL-554 • YM-976
PDE5
Acetildenafil • Aildenafil • Avanafil • Dipyridamole • Icariin • Lodenafil • Mirodenafil • MY-5445 • Sildenafil • Sulfoaildenafil • T-0156 • Tadalafil • Udenafil • Vardenafil
PDE6
Zaprinast
PDE7
BRL-50481
PDE9
BAY 73-6691 • SCH-51866
PDE10
Papaverine • PF-2545920 • Tofisopam
Nonselective

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  • PAPAVÉRINE — Alcaloïde de formule brute C20H214N, que l’on trouve en faible quantité dans l’opium (environ 0,01 p. 100 des alcaloïdes totaux de celui ci) extrait d’une variété de pavot, Papaver somniferum , de la famille des papavéracées. Produit très toxique …   Encyclopédie Universelle

  • Papaverine — Papavérine Papavérine Structure de la papavérine Général Nom IUPAC 1 [(3,4 diméthoxyphényl)méthyl] 6,7 diméthoxy isoquinol …   Wikipédia en Français

  • Papavérine — Structure de la papavérine Général Nom IUPAC 1 [(3,4 diméthoxyphényl)méthyl] 6,7 diméthoxy isoquinoline …   Wikipédia en Français

  • Papaverine — Pa*pav er*ine, n. (Chem.) An alkaloid found in opium. It has a weaker therapeutic action than morphine. [1913 Webster] …   The Collaborative International Dictionary of English

  • papaverine — [pə pav′ər ēn΄, pə pav′ər in; pəpāv′ər ēn΄ pəpāv′ər in] n. [L papaver, poppy + INE3] a white, crystalline alkaloid, C20H21NO4, derived from opium and used in medicine to relax muscles in spasms and as a local anesthetic …   English World dictionary

  • papaverine — A benzylisoquinoline alkaloid of opium that is not a narcotic but has mild analgesic action and is a powerful spasmolytic; does not evoke tolerance and has no addiction liability; used to treat male impotence by local …   Medical dictionary

  • papaverine — n. an alkaloid, derived from opium, that relaxes smooth muscle. In combination with morphine and codeine (a mixture called papaveretum), it is administered by injection as a preanaesthetic medication and for relief of postoperative pain, but is… …   The new mediacal dictionary

  • papaverine hydrochloride — papaverine hydrochloride, a white, slightly bitter powder, a non habit forming narcotic, used to relax smooth muscles. Formula: C20H21NO4•HCl …   Useful english dictionary

  • papaverine — noun Etymology: International Scientific Vocabulary, from Latin papaver poppy Date: 1857 a crystalline alkaloid C20H21NO4 found in opium or made synthetically that is used usually in the form of its hydrochloride chiefly as an antispasmodic for… …   New Collegiate Dictionary

  • papaverine — Constituent of opium that acts as a smooth muscle relaxant probably by blocking membrane calcium channels and inhibiting phosphodiesterase …   Dictionary of molecular biology

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