In addition to opium, papaverine is purported to be present in high concentrations in star gooseberry.[1]
History
Papaverine was discovered in 1848 by Georg Merck (1825–1873).[2] 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.[3]
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.
Papaverine is found as a contaminant in some heroin[17] and can be used by forensic laboratories in heroin profiling to identify its source.[18] The metabolites can also be found in the urine of heroin users, allowing street heroin to be distinguished from pharmaceutical diacetylmorphine.[19]
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[clarification needed] levels is significant. It may also alter mitochondrialrespiration.
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,[20][21] although not all studies support this view.[22]
Papaverine is available in its salt form as the hydrochloride, codecarboxylate, adenylate, and teprosylate. 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. 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[25]), 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] In Hungary, papaverine and homatropine methylbromide are used in mild drugs that help "flush" the bile.[26]
References
^Kao CH; Ho YJ; Wu CL; ChangLai SP (1999). "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. 66 (1). Karger AG: 46–51. doi:10.1159/000029336. PMID9973690. S2CID38378580.
^Kim ED, el-Rashidy R, McVary KT (February 1995). "Papaverine topical gel for treatment of erectile dysfunction". The Journal of Urology. 153 (2): 361–365. doi:10.1097/00005392-199502000-00019. PMID7815584.
^Müller-Schweinitzer E, Ellis P (May 1992). "Sucrose promotes the functional activity of blood vessels after cryopreservation in DMSO-containing fetal calf serum". Naunyn-Schmiedeberg's Archives of Pharmacology. 345 (5): 594–597. doi:10.1007/bf00168954. PMID1528275. S2CID10441842.
^Müller-Schweinitzer E, Hasse J, Swoboda L (1993). "Cryopreservation of human bronchi". The Journal of Asthma. 30 (6): 451–457. doi:10.3109/02770909309056754. PMID8244915.
^Brockbank KG (February 1994). "Effects of cryopreservation upon vein function in vivo". Cryobiology. 31 (1): 71–81. doi:10.1006/cryo.1994.1009. PMID8156802.
^Strang J, Metrebian N, Lintzeris N, Potts L, Carnwath T, Mayet S, et al. (May 2010). "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. 375 (9729): 1885–1895. doi:10.1016/s0140-6736(10)60349-2. PMID20511018. S2CID205958031.
^Siuciak JA, Chapin DS, Harms JF, Lebel LA, McCarthy SA, Chambers L, et al. (August 2006). "Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis". Neuropharmacology. 51 (2): 386–396. doi:10.1016/j.neuropharm.2006.04.013. PMID16780899. S2CID13447370.
^Hebb AL, Robertson HA, Denovan-Wright EM (May 2008). "Phosphodiesterase 10A inhibition is associated with locomotor and cognitive deficits and increased anxiety in mice". European Neuropsychopharmacology. 18 (5): 339–363. doi:10.1016/j.euroneuro.2007.08.002. PMID17913473. S2CID9621541.