During a shortage of papaverine, a drug used for surgery on blood vessels, the clinic produced its own version.
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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. 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.
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Denaverine, like papaverine, acts as a phosphodiesterase inhibitor. Additionally, it has anticholinergic effects.
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An intracavernous (or intracavernosal) injection is an injection into the base of the penis. This injection site is often used to administer medications to check for or treat erectile dysfunction in adult men (in e.g. combined intracavernous injection and stimulation test). The more common medications administered in this manner include Caverject, Trimix (prostaglandin, papaverine, and phentolamine), Bimix (papaverine and phentolamine), and Quadmix (prostaglandin, papaverine, phentolamine, and either atropine or forskolin).
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Phosphodiesterase type 10 (PDE10) is a type of phosphodiesterase enzyme. Some inhibitors include papaverine, PF-2545920, TC-E 5005, and tofisopam.
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It is a second generation papaverine analog, and was first synthesized around the same time as verapamil. It was first registered in 1965.
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The major cost is that it must be mixed by a compounding pharmacy and supplies may be difficult to obtain. The different formulations, including Bimix and Trimix, may include papaverine and/or phentolamine. A typical mix might be 30 mg of papaverine, 2 mg of phentolamine, and 20 μg alprostadil. As a generic, it is much less expensive than the packaged injectables.
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Capsule of Papaver somniferum showing latex (opium) exuding from incision. Papaverine occurs naturally in opium. 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.
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Hönigschmid studied at the gymnasium in Olomouc, then at the Charles University in Prague under the guidance of Guido Goldschmiedt (the discoverer of the structure of papaverine).
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Papaverine (Latin papaver, "poppy") is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasm and vasospasm (especially those involving the intestines, heart, or brain), and occasionally in the treatment of erectile dysfunction. It is used in the treatment of acute mesenteric ischemia. While it is found in the opium poppy, papaverine differs in both structure and pharmacological action from the analgesic morphine-like compounds.
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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. 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. Papaverine in the plant Sauropus androgynus is linked to bronchiolitis obliterans.
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1-Benzylisoquinoline is the structural backbone in naturally occurring alkaloids including papaverine. The isoquinoline ring in these natural compound derives from the aromatic amino acid tyrosine.Gilchrist, T.L. (1997). Heterocyclic Chemistry (3rd ed.).
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Both species contain morphine and papaverine, powerful opiates. Several other medicinal parallels between the two cultures exist, including the use of diterpenoids and flavones to treat skin irritations and flavonols and tannins for diarrhea.
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It is used, in addition to papaverine, as a component of mild drugs that help "flush" the bile. Certain preparations of drugs such as hydrocodone are mixed with a small, sub-therapeutic amount of homatropine methylbromide to discourage intentional overdose.
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The mineral indralite and the mercury-containing stupp (stupp is a mixture of mercury, dust, soot and unreacted ore produced in the mercury smeltering process) produced from it became the starting point for his research of polycyclic aromatic hydrocarbons, especially the two compounds idryle and pyrene. This research took most of his time between 1877 and 1883. In the following five years, Goldschmiedt focused on the determination of the structure of papaverine – a compound found in poppy seed and opium. With his 9th publication on that topic in 1889, he concluded that the structure of papaverine had been solved.
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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.
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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. 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.
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There is no antidote for palytoxin. Only the symptoms can be alleviated. Animal studies have shown that vasodilators, such as papaverine and isosorbide dinitrate, can be used as antidotes. The animal experiments only showed benefit if the antidotes were injected into the heart immediately following exposure.
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Because of its reliance on CYP3A4, reboxetine O-desethylation is markedly inhibited by papaverine and ketoconazole. It weakly inhibits CYP2D6 and CYP3A4. Reboxetine is an intermediate-level inhibitor of P-glycoprotein, which gives it the potential to interact with ciclosporin, tacrolimus, paroxetine, sertraline, quinidine, fluoxetine, fluvoxamine.
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Laudanosine also occurs naturally in minute amounts (0.1%) in opium, from which it was first isolated in 1871. Retrieved September 18, 2008 through Google Book Search. Partial dehydrogenation of laudanosine will lead to papaverine, the alkaloid found in the opium poppy plant (Papaver somniferum). Laudanosine is a benzyltetrahydroisoquinoline alkaloid.
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Papaverine, in contrast, has an antispasmodic effect if it comes from smooth muscles, as is the case in humans in the gastrointestinal tract or blood vessels. This is why it is used as an antispasmodic.Franz v. Bruchhausen, Gerd Dannhardt, Siegfried Ebel, August-Wilhelm Frahm, Eberhard Hackenthal, Ulrike Holzgrabe: Hagers Handbuch der Pharmazeutischen Praxis. 5. Auflage.
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Guido Goldschmiedt (May 29, 1850 – August 6, 1915) was an Austrian chemist. During his career, he collaborated with Bunsen in Heidelberg and Baeyer in Straßburg. In 1891, he became full professor at the University of Vienna and later at the University of Prague. His most remarkable results were establishing the structure of several natural compounds including papaverine and ellagic acid.
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Trimix is an injectable three-drug prescribed medication used to treat erectile dysfunction. The active ingredients in the mixture are usually alprostadil, papaverine, and phentolamine. The injection must be compounded by a pharmacy and administered via intracavernosal injection (an injection at either side, not the base, of the penis). Trimix is typically compounded by a pharmacy in a sterile environment and then frozen.
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Recognition that the knowledge about PDE could be used to develop drugs that were PDE inhibitors led to extensive research. Most studies used analogues of the nucleotide substrates or derivatives of natural product inhibitors such as xanthine (e.g. theophylline) and papaverine. The active site of PDE3 can be considered as a summary of ideas about receptor topography resulting from the first generation inhibitors.
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A topical gel is also available for ED treatment. 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. Papaverine is also being investigated as a topical growth factor in tissue expansion with some success.
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Drotaverine (INN, also known as drotaverin) is an antispasmodic drug, used to enhance cervical dilation during childbirth.Padubidri V and Anand E. Title Textbook of Obstetrics. BI Publications Pvt Ltd, 2006 It is structurally related to papaverine, is a selective inhibitor of phosphodiesterase 4, and has no anticholinergic effects. It is available in Asian and Central and Eastern European countries under several brand names.
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Carl Ulrich Franz Mannich (March 8, 1877 in Breslau - March 5, 1947 in Karlsruhe) was a German chemist. From 1927 to 1943 he was professor for pharmaceutical chemistry at the University of Berlin. His areas of expertise were keto bases, alcohol bases, derivatives of piperidine, papaverine, lactones and also Digitalis-glycosides. The Mannich reaction was named after his discovery of the mechanism in 1912.
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Opium tincture is useful as an analgesic and antidiarrheal. Opium enhances the tone in the long segments of the longitudinal muscle and inhibits propulsive contraction of circular and longitudinal muscles. The pharmacological effects of opium tincture are due principally to its morphine content. The quantity of the papaverine and codeine alkaloids in opium tincture is too small to have any demonstrable central nervous system effect.
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Opium contains two main groups of alkaloids. Phenanthrenes such as morphine, codeine, and thebaine are the main psychoactive constituents. Isoquinolines such as papaverine and noscapine have no significant central nervous system effects. Morphine is the most prevalent and important alkaloid in opium, consisting of 10–16 percent of the total, and is responsible for most of its harmful effects such as lung edema, respiratory difficulties, coma, or cardiac or respiratory collapse.
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Metofoline (INN), also known as methofoline (USAN), is an opioid analgesic drug discovered in the 1950s by a team of Swiss researchers at Hoffmann-La Roche. Methopholine is an isoquinoline derivative which is not structurally related to most other opioids. However, its structural similarity to the non- opioid alkaloid papaverine is notable. Metofoline has around the same efficacy as an analgesic as codeine, and was evaluated for the treatment of postoperative pain.
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Papaveretum (BAN) is a preparation containing a mixture of hydrochloride salts of opium alkaloids. Since 1993, papaveretum has been defined in the British Pharmacopoeia (BP) as a mixture of 253 parts morphine hydrochloride, 23 parts papaverine hydrochloride, and 20 parts codeine hydrochloride. It is commonly marketed to medical agencies under the trade name Omnopon. Although the use of papaveretum is now relatively uncommon following the wide availability of single-component opiates and synthetic opioids (e.g.
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Codeine Chemical structure of morphine Opiates belong to the large biosynthetic group of benzylisoquinoline alkaloids, and are so named because they are naturally occurring alkaloids found in the opium poppy. The major psychoactive opiates are morphine, codeine, and thebaine. Papaverine, noscapine, and approximately 24 other alkaloids are also present in opium but have little to no effect on the human central nervous system. Alkaloids that have no effect on the central nervous system are not considered to be opiates.
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During coronary catheterization, a catheter is inserted into the femoral (groin) or radial arteries (wrist) using a sheath and guidewire. FFR uses a small sensor on the tip of the wire (commonly a transducer) to measure pressure, temperature and flow to determine the exact severity of the lesion. This is done during maximal blood flow (hyperemia), which can be induced by injecting products such as adenosine or papaverine. A pullback of the pressure wire is performed, and pressures are recorded across the vessel.
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Substitution of the heterocycle isoquinoline at the C1 position by a benzyl group provides 1‑benzylisoquinoline, the most widely examined of the numerous benzylisoquinoline structural isomers. The 1-benzylisoquinoline moiety can be identified within numerous compounds of pharmaceutical interest, such as moxaverine; but most notably it is found within the structures of a wide variety of plant natural products, collectively referred to as benzylisoquinoline alkaloids. This class is exemplified in part by the following compounds: papaverine, noscapine, codeine, morphine, apomorphine, berberine, tubocurarine.
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Codeine, or 3-methylmorphine, is an alkaloid found in the opium poppy, Papaver somniferum var. album, a plant in the family Papaveraceae. Opium poppy has been cultivated and utilized throughout human history for a variety of medicinal (analgesic, anti-tussive and anti-diarrheal) and hypnotic properties linked to the diversity of its active components, which include morphine, codeine and papaverine. Codeine is found in concentrations of 1% to 3% in opium prepared by the latex method from unripe pods of Papaver somniferum.
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Poppy tea contains two groups of alkaloids: phenanthrenes (including morphine and codeine) and benzylisoquinolines (including papaverine). Of these, morphine is the most prevalent comprising 8%-14% of the total. Its effects derive from the fact that it binds to and activates mu opioid receptors in the brain, spinal cord, stomach and intestine. Dried Papaver somniferum capsules and stems will, if harvested and dried by the usual protocol, contain significantly lower quantities of thebaine than opium made from latex as well as somewhat more codeine.
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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. 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.
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Causes of low flow priapism include sickle cell anemia (most common in children), leukemia, and other blood dyscrasias such as thalassemia and multiple myeloma, and the use of various drugs, as well as cancers. Other conditions such as Fabry's disease, as well as neurologic disorders such as spinal cord lesions and spinal cord trauma (priapism has been reported in people who have been hanged; see death erection). Priapism can also be caused by reactions to medications. The most common medications that cause priapism are intra-cavernous injections for the treatment of erectile dysfunction (papaverine, alprostadil).
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Lavoisier showed at the end of the 18th century that organic substances consisted of a limited number of elements: primarily carbon and hydrogen and supplemented by oxygen and nitrogen. He quickly focused on the isolation of these substances, often because they had an interesting pharmacological activity. Plants were the main source of such compounds, especially alkaloids and glycosides. It was long been known that opium, a sticky mixture of alkaloids (including codeine, morphine, noscapine, thebaine, and papaverine) from the opium poppy (Papaver somniferum), possessed a narcotic and at the same time mind-altering properties.
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The resulting 1-substituted 3,4-dihydroisoquinoline can then be dehydrogenated using palladium. The following Bischler–Napieralski reaction produces papaverine. 800px The Pictet–Gams reaction and the Pictet–Spengler reaction are both variations on the Bischler–Napieralski reaction. A Pictet–Gams reaction works similarly to the Bischler–Napieralski reaction; the only difference being that an additional hydroxy group in the reactant provides a site for dehydration under the same reaction conditions as the cyclization to give the isoquinoline rather than requiring a separate reaction to convert a dihydroisoquinoline intermediate.
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A man who is able to get an erection but has trouble maintaining it for long enough can use a ring by itself. The ring cannot be left on for more than 30 minutes and cannot be used at the same time as anticoagulant medications. If oral medications and mechanical treatments fail, the second choice is local injections: medications such as papaverine and prostaglandin that alter the blood flow and trigger erection are injected into the penis. This method is preferred for its effectiveness, but can cause pain and scarring.
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Latex from the chicle and jelutong trees was used in chewing gum. Dried latex from the opium poppy is called opium, the source of several useful analgesic alkaloids such as codeine, thebaine, and morphine, the latter two of which can then further be used in the synthesis and manufacture of other (typically stronger) opioids for medicinal use, and of heroin for the illegal drug trade. The opium poppy is also the source of medically useful non-analgesic alkaloids, such as papaverine and noscapine. Synthetic latexes are used in coatings (e.g.
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Since the diamorphine in street heroin is the same as the pharmaceutical diamorphine, examination of the contaminants is the only way to test whether street heroin has been used. Other contaminants used in urine samples alongside noscapine include papaverine and acetylcodeine. Noscapine is metabolised by the body, and is itself rarely found in urine, instead being present as the primary metabolites, cotarnine and meconine. Detection is performed by gas chromatography-mass spectrometry or liquid chromatography- mass spectrometry (LCMS) but can also use a variety of other analytical techniques.
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The PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken by mouth. As of 2018, sildenafil is available in the UK without a prescription. Additionally, a cream combining alprostadil with the permeation enhancer DDAIP has been approved in Canada as a first line treatment for ED. Penile injections, on the other hand, can involve one of the following medications: papaverine, phentolamine, and prostaglandin E1, also known as alprostadil. In addition to injections, there is an alprostadil suppository that can be inserted into the urethra.
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Modern drug therapy for ED made a significant advance in 1983, when British physiologist Giles Brindley dropped his trousers and demonstrated to a shocked Urodynamics Society audience his papaverine-induced erection. The drug Brindley injected into his penis was a non-specific vasodilator, an alpha-blocking agent, and the mechanism of action was clearly corporal smooth muscle relaxation. The effect that Brindley discovered established the fundamentals for the later development of specific, safe, and orally effective drug therapies. The current first-line treatment for ED, the oral PDE5 inhibitor, was introduced by Pfizer in 1999.
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The British physician James W. Black developed beta blockers in the early 1960s; these were initially used for angina, but turned out to lower blood pressure. Black received the 1976 Lasker Award and in 1988 the Nobel Prize in Physiology or Medicine for his discovery. The next class of antihypertensives to be discovered were calcium channel blockers. The first member was verapamil, a derivative of papaverine that was initially thought to be a beta blocker and used for angina, but then turned out to have a different mode of action and was shown to lower blood pressure.
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It is a good source of vitamin K. However, a study has suggested that excessive consumption of juiced Katuk leaves (due to its popularity for body weight control in Taiwan in the mid '90s) can cause lung damage, due to its high concentrations of the alkaloid papaverine. It also has high level of provitamin A carotenoids, especially in freshly picked leaves, as well as high levels of vitamins B and C, protein and minerals. The more the leaves mature, the higher the nutrient content of the leaves.19.1 Sauropus androgynus (sweet leaf bush) It is common in evergreen forest and cultivated up to 1,300 m.
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Opium (or poppy tears, scientific name: Lachryma papaveris) is dried latex obtained from the seed capsules of the opium poppy Papaver somniferum. Approximately 12 percent of opium is made up of the analgesic alkaloid morphine, which is processed chemically to produce heroin and other synthetic opioids for medicinal use and for the illegal drug trade. The latex also contains the closely related opiates codeine and thebaine, and non-analgesic alkaloids such as papaverine and noscapine. The traditional, labor-intensive method of obtaining the latex is to scratch ("score") the immature seed pods (fruits) by hand; the latex leaks out and dries to a sticky yellowish residue that is later scraped off and dehydrated.
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Mardepodect (developmental code name PF-2545920) is a drug which was developed by Pfizer for the treatment of schizophrenia. It acts as a phosphodiesterase inhibitor selective for the PDE10A subtype. The PDE10A enzyme is expressed primarily in the brain, mostly in the striatum, nucleus accumbens and olfactory tubercle, and is thought to be particularly important in regulating the activity of dopamine-sensitive medium spiny neurons in the striatum which are known to be targets of conventional antipsychotic drugs. Older PDE10A inhibitors such as papaverine have been shown to produce antipsychotic effects in animal models, and more potent and selective PDE10A inhibitors are a current area of research for novel antipsychotic drugs which act through a different pathway to conventional dopamine or 5-HT2A antagonist drugs and may have a more favourable side effects profile.
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A.H.Bennett Impotence Saunders (v. dédicace de l’ouvrage et page 209) In 1981, during a surgical procedure on the penis, he discovered that an old medication extracted from poppies, and used since the late 19th century to dilate blood vessels, could induce an erection when injected into the penis. After a year of observing the effects of papaverine on volunteers, among which himself, the discovery is being published in the famous medical journal “Lancet”.R.Virag Intracavnous Injection for erectile failure Lancet 1982 2 : 938 From then on nothing will ever be the same again, neither in the treatment, as quite rapidly a thousand of patients will benefit from it, or in research as the intracavernous injection will now be the reference and the means of triggering the erection when needed to be studied.
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