Papaverine

Overview

Papaverine (Latin papaver, "poppy") is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasms and vasospasms (especially those involving the intestines, heart, or brain), occasionally in the treatment of erectile dysfunction and acute mesenteric ischemia. While it is found in the opium poppy, papaverine differs in both structure and pharmacological action from the analgesic morphine and its derivatives (such as codeine). WP

One study has suggested that excessive consumption of uncooked katuk leaves can cause lung damage due to the high concentrations of papaverine present.[1] WP

Uses, dosage and effects

Uses

Papaverine is approved to treat spasms of the gastrointestinal tract, bile ducts and ureter and for use as a cerebral and coronary vasodilator in subarachnoid hemorrhage (combined with balloon angioplasty) and coronary artery bypass surgery. Papaverine may also be used as a smooth muscle relaxant in microsurgery where it is applied directly to blood vessels.[2][3] WP

Papaverine is used as an erectile dysfunction drug, alone or sometimes in combination. 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][5][6] WP

It is also commonly used in cryopreservation of blood vessels along with the other glycosaminoglycans and protein suspensions. Functions as a vasodilator during cryopreservation when used in conjunction with verapamil, phentolamine, nifedipine, tolazoline or nitroprusside.[7–10] WP

Papaverine is also being investigated as a topical growth factor in tissue expansion with some success.[11] WP

Papaverine is used as an off-label prophylaxis (preventative) of migraine headaches. 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.[12][13][14] WP

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. WP

Papaverine is found as a contaminant in some heroin and can be used by forensic laboratories in heroin profiling to identify its source. The metabolites can also be found in the urine of heroin users, allowing street heroin to be distinguished from pharmaceutical diacetylmorphine.[15][16][17] WP

Risks and side effects

Side effects

Frequent side effects of papaverine treatment include polymorphic ventricular tachycardia, constipation, interference with sulphobromophthalein retention test (used to determine hepatic function), increased transaminase levels, increased alkaline phosphatase levels, somnolence, and vertigo. WP⚠ Wikipedia itself has flagged this text: citation needed.

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, and paradoxical aggravation of cerebral vasospasm.[18] WP

High doses of papaverine have been linked to bronchiolitis obliterans.[19] WP

Pharmacology

Mechanism

The in vivo mechanism of action is not entirely clear, but an inhibition of the enzyme phosphodiesterase causing elevation of cyclic AMP and cyclic GMP levels is significant. It may also alter mitochondrial respiration. WP⚠ Wikipedia itself has flagged this text: clarification needed.⚠ A word may be missing here. It reads this way in the source too.

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, although not all studies support this view.[20][21][22] WP

History

History

Papaverine was discovered in 1848 by Georg Merck (1825–1873). Merck was a student of the German chemists Justus von Liebig and August Hofmann, and he was the son of Emanuel Merck (1794–1855), founder of the Merck corporation, a major German chemical and pharmaceutical company.[23][24] WP

Chemistry

Formula

C20H21NO4 PC

CAS number

58-74-2 PC

Molar mass (g/mol)

339.4 PC

IUPAC name (computed by PubChem)

1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline PC

SMILES

COC1=C(C=C(C=C1)CC2=NC=CC3=CC(=C(C=C32)OC)OC)OC PC

InChIKey

XQYZDYMELSJDRZ-UHFFFAOYSA-N PC

PubChem CID

4680

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Kao CH, Ho YJ, Wu CL, ChangLai SP. Using 99mTc-DTPA radioaerosol inhalation lung scintigraphies to detect the lung injury induced by consuming Sauropus androgynus vegetable and comparison with conventional pulmonary function tests. Respiration; International Review of Thoracic Diseases. 1999. doi:10.1159/000029336 · PMID 9973690
2. Journal / agency Liu JK, Couldwell WT. Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage. Neurocritical Care. 2005. doi:10.1385/NCC:2:2:124 · PMID 16159054
3. Journal / agency Takeuchi K, Sakamoto S, Nagayoshi Y, Nishizawa H, Matsubara J. Reactivity of the human internal thoracic artery to vasodilators in coronary artery bypass grafting. European Journal of Cardio-Thoracic Surgery. November 2004. doi:10.1016/j.ejcts.2004.07.047 · PMID 15519189
4. Journal / agency Desvaux P. An overview of the management of erectile disorders. Presse Médicale. July 2005. PMID 16158020
5. Journal / agency Bella AJ, Brock GB. Intracavernous pharmacotherapy for erectile dysfunction. Endocrine. 2004. doi:10.1385/ENDO:23:2-3:149 · PMID 15146094
6. Journal / agency Kim ED, el-Rashidy R, McVary KT. Papaverine topical gel for treatment of erectile dysfunction. The Journal of Urology. February 1995. doi:10.1097/00005392-199502000-00019 · PMID 7815584
7. Journal / agency Müller-Schweinitzer E, Ellis P. Sucrose promotes the functional activity of blood vessels after cryopreservation in DMSO-containing fetal calf serum. Naunyn-Schmiedeberg's Archives of Pharmacology. May 1992. doi:10.1007/bf00168954 · PMID 1528275
8. Journal / agency Müller-Schweinitzer E, Hasse J, Swoboda L. Cryopreservation of human bronchi. The Journal of Asthma. 1993. doi:10.3109/02770909309056754 · PMID 8244915
9. Journal / agency Brockbank KG. Effects of cryopreservation upon vein function in vivo. Cryobiology. February 1994. doi:10.1006/cryo.1994.1009 · PMID 8156802
10. Journal / agency Giglia JS, Ollerenshaw JD, Dawson PE, Black KS, Abbott WM. Cryopreservation prevents arterial allograft dilation. Annals of Vascular Surgery. November 2002. doi:10.1007/s10016-001-0072-1 · PMID 12391500
11. Journal / agency Tang Y, Luan J, Zhang X. Accelerating tissue expansion by application of topical papaverine cream. Plastic and Reconstructive Surgery. October 2004. doi:10.1097/01.PRS.0000135854.48570.76 · PMID 15457029
12. Journal / agency Sillanpää M, Koponen M. Papaverine in the prophylaxis of migraine and other vascular headache in children. Acta Paediatrica Scandinavica. March 1978. doi:10.1111/j.1651-2227.1978.tb16304.x · PMID 343489
13. Journal / agency Vijayan N. Brief therapeutic report: papaverine prophylaxis of complicated migraine. Headache. September 1977. doi:10.1111/j.1526-4610.1977.hed1704159.x · PMID 893088
14. Journal / agency Poser CM. Letter: Papaverine in prophylactic treatment of migraine. Lancet. June 1974. doi:10.1016/S0140-6736(74)90045-2 · PMID 4134173
15. Journal / agency Paterson S, Cordero R. Comparison of the various opiate alkaloid contaminants and their metabolites found in illicit heroin with 6-monoacetyl morphine as indicators of heroin ingestion. Journal of Analytical Toxicology. May 2006. doi:10.1093/jat/30.4.267 · PMID 16803666
16. Journal / agency Seetohul LN, Maskell PD, De Paoli G, Pounder DJ. Biomarkers for illicit heroin: a previously unrecognized origin of papaverine. Journal of Analytical Toxicology. March 2013. doi:10.1093/jat/bks099 · PMID 23316026
17. Journal / agency Strang J, Metrebian N, Lintzeris N, Potts L, Carnwath T, Mayet S, Williams H, Zador D, Evers R, Groshkova T, Charles V, Martin A, Forzisi L. Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial. Lancet. May 2010. doi:10.1016/s0140-6736(10)60349-2 · PMID 20511018
18. Journal / agency Clyde BL, Firlik AD, Kaufmann AM, Spearman MP, Yonas H. Paradoxical aggravation of vasospasm with papaverine infusion following aneurysmal subarachnoid hemorrhage. Case report. Journal of Neurosurgery. April 1996. doi:10.3171/jns.1996.84.4.0690 · PMID 8613866
19. Journal / agency Bunawan H, Bunawan SN, Baharum SN, Noor NM. Sauropus androgynus (L.) Merr. Induced Bronchiolitis Obliterans: From Botanical Studies to Toxicology. Evidence-Based Complementary and Alternative Medicine. 2015. doi:10.1155/2015/714158 · PMID 26413127 · PMC4564651
20. Journal / agency Siuciak JA, Chapin DS, Harms JF, Lebel LA, McCarthy SA, Chambers L, Shrikhande A, Wong S, Menniti FS, Schmidt CJ. Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis. Neuropharmacology. August 2006. doi:10.1016/j.neuropharm.2006.04.013 · PMID 16780899
21. Journal / agency Hebb AL, Robertson HA, Denovan-Wright EM. Phosphodiesterase 10A inhibition is associated with locomotor and cognitive deficits and increased anxiety in mice. European Neuropsychopharmacology. May 2008. doi:10.1016/j.euroneuro.2007.08.002 · PMID 17913473
22. Journal / agency Weber M, Breier M, Ko D, Thangaraj N, Marzan DE, Swerdlow NR. Evaluating the antipsychotic profile of the preferential PDE10A inhibitor, papaverine. Psychopharmacology. May 2009. doi:10.1007/s00213-008-1419-x · PMID 19066855 · PMC2748940
23. Journal / agency Merck G. Vorläufige Notiz über eine neue organische Base im Opium. Annalen der Chemie und Pharmacie. 1848. doi:10.1002/jlac.18480660121
24. Other Brock WH. Justus Von Liebig: The Chemical Gatekeeper. 2002-06-20

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.