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PAPAVERINE HYDROCHLORIDE

PAPAVERINE HYDROCHLORIDE Basic information
Product Name:PAPAVERINE HYDROCHLORIDE
Synonyms:AKOS 220-12;1-((3,4-dimethoxyphenyl)methyl)-6,7-dimethoxy-isoquinolin;1-((3,4-Dimethoxyphenyl)methyl)-6,7-dimethoxyisoquinoline;6,7-dimethoxy-1-veratryl-isoquinolin;6,7-Dimethoxy-1-veratrylisoquinoline;Isoquinoline, 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-;Isoquinoline, 6,7-dimethoxy-1-veratryl-;papanerin
CAS:58-74-2
MF:C20H21NO4
MW:339.39
EINECS:200-397-2
Product Categories:
Mol File:58-74-2.mol
PAPAVERINE HYDROCHLORIDE Structure
PAPAVERINE HYDROCHLORIDE Chemical Properties
Melting point 226 °C
Boiling point 475.36°C (rough estimate)
density d420 1.337
refractive index 1.6250 (estimate)
solubility H2O: 25 mg/mL
pka6.4(at 25℃)
form powder
color white
Water Solubility 37.33mg/L(37.5 ºC)
Merck 14,7019
BRN 312930
Safety Information
Hazard Codes Xn
Risk Statements 22
Safety Statements 22
RIDADR UN 1544 6.1/PG 3
WGK Germany 1
RTECS NW8575000
8
HazardClass 6.1(a)
PackingGroup II
Hazardous Substances Data58-74-2(Hazardous Substances Data)
ToxicityLD50 orl-rat: 325 mg/kg ARZNAD 20,1338,70
MSDS Information
ProviderLanguage
ACROS English
SigmaAldrich English
ALFA English
PAPAVERINE HYDROCHLORIDE Usage And Synthesis
Chemical PropertiesWhite crystalline powder; obtained asorthorhombic prisms from an alcohol–ethermixture; melts at 147°C (296.6°F); sublimesunder vacuum; insoluble in water; soluble inacetone, glacial acetic acid, and benzene.
OriginatorLempav Ty-Med ,Lemmon,US,1975
UsesPapaverine occurs in opium to the extent of0.8–1.0%, commonly associated with narcotine.It is used as a smooth muscle relaxantand in medicine for its vasodilator action onthe blood vessels in the brain. It is effectiveagainst asthma.
Usesmuscle relaxant (smooth), cerebral vasodilator
Usesfolate metabolic inhibitor, coccidiostat
Usesopium alkaloid
DefinitionChEBI: A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum.
IndicationsPapaverine (Pavabid) is a nonspecific phosphodiesterase inhibitor that increases cAMP and cGMP levels in penile erectile tissue. Papaverine is particularly known as a smooth muscle relaxant and vasodilator. Its principal pharmacological action is as a nonspecific vasodilator of smooth muscles of the arterioles and capillaries. Various vascular beds and smooth muscle respond differently to papaverine administration both in intensity and duration. Papaverine decreases the resistance to arterial inflow and increases the resistance to venous outflow.
Manufacturing ProcessTo 3.65 g (0.01 mol) of monohydrated adenosine-5'-monophosphoric acid, brought into suspension in a mixture of 45 ml of water and 5 ml of ethanol, are added 339 g (0.01 mol) of papaverine base (melting point, 147°C). The mixture is gently heated until a final temperature of 40°C is reached. The solution obtained is then filtered and the filtrate is concentrated under vacuum. The remaining product quickly crystallizes. After drying to 50°C to constant weight, there are obtained 6.68 g of desired product, in the monohydrated state, as a white crystalline powder, which melts at 140°C and is very soluble in water.
Brand namePavabid (Hoechst Marion Roussel).
Therapeutic FunctionVasodilator, Platelet aggregation inhibitor
Health HazardPapaverine is an inhibitor of cyclic nucleotidephosphodiesterase, producing vasodilatoryeffect. The acute toxic effects relative tophenanthrene-type opium alkaloids (e.g.,morphine, heroin) are low and the symptomsare not the same. Papaverine is neither a narcoticnor an addictive substance. Excessivedoses may produce drowsiness, headache,facial flushing, constipation, nausea, vomiting,and liver toxicity.
The LD50 data reported in the literatureshow variation. An oral LD50 value in rats ison the order of 400 mg/kg.
Mechanism of actionWhen administered by intracavernosal injection, papaverine, a weak and nonspecific PDE inhibitor, is thought to cause relaxation of the cavernous smooth muscles and vasodilation of the penile arteries by inhibition of PDE. These effects result in increased arterial blood flow into the corpus cavernosa and in swelling and elongation of the penis. Venous outflow also is reduced, possibly as a result of increased venous resistance.
Clinical UsePapaverine is highly effective in men with psychogenic and neurogenic ED but less effective in men with vasculogenic ED. Papaverine–phentolamine combinations have been used in self-injection procedures. Papaverine doses may range from 15 to 60 mg. Papaverine treatment in patients with severe arterial or venous incompetence is usually unsuccessful, but autoinjections using low doses sufficient to achieve an erection are safe and efficient.
Side effectsMajor side effects associated with papaverine therapy include priapism, corporeal fibrosis, and occasional increases in serum aminotransferases. Intracorporeal scarring may be related to the low pH of the vehicle that is necessary to solubilize papaverine.Attempts to buffer papaverine to render it more suitable for intracavernosal injection have not been entirely satisfactory, and such delivery may still lead to intracorporeal scarring.
Safety ProfilePoison by ingestion, intramuscular, subcutaneous, intradermal, intraperitoneal, and intravenous routes. Human systemic effects: coma, somnolence. Its central nervous system action is about midway between those of morphme and codeine, and large doses do not produce the amount of excitement caused by codeine or the soporific action of morphine. Mutation data reported. A cerebral vasodilator and smooth muscle relaxant. Combustible when exposed to heat or flame. When heated to decomposition it emits toxic fumes of NOx. See also MORPHINE.
SynthesisPapaverine, 1-veratryl-6,7-dimethoxyisoquinolin (19.4.7), is synthesized from veratrol. Veratrol undergoes chloromethylation, forming 3,4-dimethoxybenzylchloride (19.4.1). Reacting this with potassium cyanide gives 3,4-dimethoxybenzylcyanide (19.4.2). The resulting 3,4-dimethoxybenzylcyanide undergoes reduction by hydrogen over Raney nickel, forming homoveratrylamine (19.4.3). At the same time 3,4-dimethoxybenzylcyanide (19.4.2) undergoes acidic hydrolysis giving 3,4-dimethoxyphenylacetic acid (19.4.4). The interaction of the resulting compounds brings to corresponding amide (19.4.5). The cyclization of this by Bischler¨CNapieralski method, using phosphorous oxychloride, gives 3,4-dihydropapaverine (19.4.6), which is dehydrated into the desired papverine when heated in tetraline at high temperatures.

Synthesis_58-74-2

Tag:PAPAVERINE HYDROCHLORIDE(58-74-2) Related Product Information
Elziverine ethaverine Papaverine hydrochloride Dimoxyline PAPAVERINE HYDROCHLORIDE Drotaverin hydrochloride R-tetrahydropapaverine HCl (+/-)-Tetrahydropapaverine R-Tetrahydropapaverine N-acetyl-L-leucinate BOLDINE DIMETHYL ETHER (R)-(+)-Tetrahydropapaverine Tetrahydropapaverine hydrochloride 1-[(3,4-Dimethoxyphenyl)methyl]-3,4-dihydro-6,7-dimethoxyisoquinoline 6,7-DIMETHOXYISOQUINOLINE 1-(2-bromo-4,5-dimethoxybenzyl)-6,7-dimethoxyisoquinoline ethaverine hydrochloride TOSLAB 11931 DIOXYLINEPHOSPHATE