Papaverine is a substance from the group of alkaloids and belongs to the active substance class of spasmolytics. The alkaloid is found in the dried milk sap of the opium poppy. However, it can also be produced synthetically.
What is papaverine?
The alkaloid is found in the dried milk sap of the opium poppy. However, it can also be produced synthetically. Papaverine is a natural substance found in the milky sap of the opium poppy and in other related poppy species. Raw opium contains about one percent papaverine. The pure substance papaverine is effective and at the same time does not have the full spectrum of possible side effects. Like the chemical papaverine derivative, papaverine is a cAMP phosphodiesterase inhibitor. It thus acts on numerous subtypes of the phosphodiesterase family. Papaverine is used primarily as a vasodilator drug. It belongs to the group of spasmolytics. Spasmolytics are antispasmodic drugs that reduce the tension state of smooth muscles and relieve their spasms. The first complete synthesis of papaverine was carried out in 1909 by the researchers Pictet and Gams. The complete structural resolution was achieved by the Austrian Guido Goldschmiedt a few years later. Pharmaceutical use today is papaverine hydrochloride as a monopreparation or in combination preparations.
Pharmacological action
Papaverine is a cAMP phosphodiesterase inhibitor. Phosphodiesterases are enzymes found in almost all tissues of the body. Any environmental change is sensed by the body and causes a stimulus. This is transmitted to the interior of the cell by messenger substances. These messenger substances are also called second messengers. The substances cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate) belong to the second messengers. They are responsible for the stimulus response in the cell. This stimulus response can occur, for example, through a change in the metabolism of the cell. Phosphodiesterases can inhibit signal transmission within the cell. Phosphodiesterases can cleave messenger substances such as cAMP or cGMP and thus render them ineffective. Phosphodiesterase inhibitors, on the other hand, interfere with the enzymes in their work and thus promote signal transmission within the cell. Papaverine is a phosphodiesterase inhibitor that inhibits phosphodiesterases that render cAMP ineffective. This prolongs the action of the neurotransmitter and enhances the effects of various stimuli. Because cAMP has a relaxing effect on smooth muscle, papaverine has antispasmodic and vasorelaxant effects.
Medicinal use and application
Papaverine is used primarily in cardiac surgery. There, the drug prevents blood vessels from spasming when harvesting arteries for bypass surgery. Papaverine is also used as an antispasmodic drug for stomach cramps, biliary colic and urinary tract spasms. However, it is increasingly being replaced by the spasmolytic propiverine for these indications, as the latter has not only antispasmodic but also anticholinergic effects. Another area of application for papaverine is male erectile dysfunction. For this purpose, the drug is injected into the corpus cavernosum of the male member. The vasodilatation then leads to increased blood flow to the penis and thus to an erection. This therapy is also known as erectile tissue auto-injection therapy (SKAT). In rare cases, papaverine is also used to treat peripheral or cerebral circulatory disorders. However, therapy with the drug is controversial for these indications.
Risks and side effects
Neurologic deficits such as hemiplegia, epileptic seizures, pupillary disturbances, or clouding of consciousness may occur when papaverine is taken. The vasodilatory effect of the drug can cause a life-threatening drop in blood pressure. In addition, intracranial pressure may increase. Overall, however, side effects occur rather rarely. However, the injection of papaverine in erectile tissue auto-injection therapy is associated with more risks. For example, painful permanent erection may occur. This form of permanent erection without arousal is called priapism. The erection lasts longer than two hours and can lead to severe erectile dysfunction if left untreated. Severe allergic reactions can also occur after papaverine injection. These take the form of skin rash, hives, chest tightness or swelling of the body.In case of these symptoms, a doctor should be consulted immediately. Excessive fatigue, cardiac arrhythmias, nausea, vomiting, and yellowing of the skin and eyes (jaundice) also require immediate medical attention. Mild side effects include diarrhea, constipation, dizziness, loss of appetite, stomach upset, or mild redness at the injection site. If these side effects persist or worsen, a doctor should also be consulted.