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

pka

6.4(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

F 

8

HazardClass 

6.1(a)

PackingGroup 

II

Hazardous Substances Data

58-74-2(Hazardous Substances Data)

Toxicity

LD50 orl-rat: 325 mg/kg ARZNAD 20,1338,70

MSDS

• Language:English Provider:SigmaAldrich
• Language:English Provider:ACROS
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PAPAVERINE HYDROCHLORIDE Usage And Synthesis

Chemical Properties

White 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.

Originator

Lempav Ty-Med ,Lemmon,US,1975

Uses

Papaverine 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.

Uses

opium alkaloid

Uses

folate metabolic inhibitor, coccidiostat

Uses

muscle relaxant (smooth), cerebral vasodilator

Definition

ChEBI: 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.

Indications

Papaverine (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 Process

To 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 name

Pavabid (Hoechst Marion Roussel).

Therapeutic Function

Vasodilator, Platelet aggregation inhibitor

Health Hazard

Papaverine 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 action

When 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 Use

Papaverine 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 effects

Major 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 Profile

Poison 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.

Synthesis

Papaverine, 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.

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