PAPAVERINE HYDROCHLORIDE

Химические свойства

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.

Использование

folate metabolic inhibitor, coccidiostat

Определение

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.

Показания

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.

Угроза здоровью

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.

Механизм действия

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.

Клиническое использование

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.

Побочные эффекты

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.

Профиль безопасности

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.