What Is Papaverine and What Is It Used For?

Papaverine is a vasodilator drug that relaxes smooth muscles in blood vessels, improving circulation. It is primarily used in the treatment of vascular spasms, peripheral artery disease, and sometimes in surgical procedures to enhance blood flow.

In neurosurgery, papaverine is applied locally to relieve cerebral vasospasm, particularly after subarachnoid hemorrhage. This improves oxygen delivery to brain tissue and reduces the risk of ischemic complications.

Papaverine may also be used in urology for erectile dysfunction management, though newer medications are preferred. Its mechanism involves direct smooth muscle relaxation without affecting central nervous system pathways.

Side effects include low blood pressure, dizziness, and gastrointestinal disturbances. Careful dosage and medical supervision are essential to minimize risks and ensure safe therapeutic outcomes.

What Is Papaverine and How Does It Work in the Body?

Papaverine is an alkaloid chemical compound. Its opium (poppy) origin may sound concerning, but unlike morphine and similar substances, papaverine does not have pain-relieving or narcotic effects, nor does it act prominently on the central nervous system or cause dependence.

Papaverine’s main action is to interrupt the chemical pathways required for smooth muscle contraction. The phosphodiesterase (PDE) enzyme within cells breaks down messenger molecules (cAMP and cGMP) involved in muscle contraction and relaxation. Papaverine inhibits this PDE enzyme—think of it as shutting a valve, so cAMP and cGMP accumulate inside the cell. This increase triggers smooth muscle relaxation and blocks contraction. As a result, blood vessels widen, blood flows more easily, and spasms are reduced.

This mechanism allows papaverine to act directly on muscle cells rather than through the brain or spinal cord. Like a firefighter intervening at the scene, it reduces local tension in muscles and supports blood flow as needed by dilating blood vessels.

How Is Papaverine Used to Treat Smooth Muscle Spasms?

Whether it’s an intestinal spasm causing abdominal pain or spasms in the bile or urinary tract, papaverine is highly effective at relieving these “cramp-like” conditions in smooth muscle. Just as loosening an overstretched elastic improves its function, papaverine relaxes contracted smooth muscle for relief.

For example, when a coronary artery goes into spasm, blood flow to the heart muscle becomes restricted, increasing the risk of chest pain (angina) or even heart attack. Papaverine’s vasodilatory action relaxes these vessels and improves blood flow. The same applies to spasms in the intestines, gallbladder, or urinary tract, where its muscle-relaxing effects bring relief.

This spasmolytic effect is related to papaverine’s inhibition of phosphodiesterase and the resulting reduction of intracellular calcium, which is crucial for muscle contraction. Lower calcium means muscle relaxation, making papaverine a go-to option for pain and dysfunction due to excessive smooth muscle contraction.

How Does Papaverine Improve Blood Flow in Circulatory Problems?

Imagine a blockage or narrowing in your circulatory system: like water struggling to pass through a narrow pipe. Papaverine acts as a “valve opener,” widening the vessels and allowing blood to flow more freely.

Scientific studies show that papaverine is particularly effective on small vessels. Even when taken sublingually (under the tongue), it can increase local blood flow without significantly affecting systemic blood pressure. In some cases—such as chronic ischemic conditions or vascular blockages—papaverine may be applied locally to maximize benefits in problem areas while minimizing side effects elsewhere.

It is also used for narrowing or spasms in cerebral arteries, increasing blood supply to brain tissue and improving oxygenation. When used in heart vessels, papaverine relieves narrowing and supports the nourishment of heart muscle. In summary, papaverine helps open blood flow wherever it’s restricted.

What Role Does Papaverine Play in the Treatment of Pulmonary Arterial Hypertension?

Pulmonary arterial hypertension (PAH) refers to high pressure in the vessels of the lungs, which places increased strain on the heart and can lead to serious heart and respiratory issues. Papaverine can relax smooth muscle in the pulmonary vessels, slightly reducing blood pressure and helping blood circulate more easily in the lungs.

However, studies show variable results—while animal studies demonstrate significant reductions in pulmonary blood pressure, human results are less consistent. Factors such as dosage, administration method, and patient health may contribute to this variation. Therefore, papaverine may not be a “miracle cure” for PAH but can be used as adjunctive or supportive therapy in selected cases.

Can Papaverine Be Used to Treat Erectile Dysfunction and How Effective Is It?

Erectile dysfunction (ED) is a common problem affecting quality of life for many men. Papaverine, through its vasodilatory effects, can increase blood flow in the penis and promote erection by relaxing smooth muscle in the vessel walls.

Historically, intracavernous papaverine injection was one of the first breakthroughs in ED treatment, relaxing smooth muscle and allowing blood to accumulate in the penis. However, the injection method is not always comfortable and carries risks such as priapism (a painful erection lasting longer than four hours). As a result, oral PDE5 inhibitors (such as sildenafil) have become more popular, but papaverine is still an option for patients who do not respond to standard treatments.

Transdermal papaverine gels have also been researched; while easier and less painful to use, they may be less potent than injections. Thus, papaverine retains a place in ED treatment, especially for resistant cases or when other medical justifications exist.

What Are the Side Effects Associated with Papaverine Use?

Like any medication, papaverine can cause side effects. The most common include gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Due to vessel dilation, low blood pressure, dizziness, and fatigue may also occur. Local reactions such as redness, swelling, or bruising may develop at injection sites.

When used for ED via injection into the penis, the risk of priapism (prolonged, painful erection) must be considered—this requires urgent medical attention. Rare side effects may include palpitations, arrhythmia, severe drops in blood pressure, or liver-related symptoms such as jaundice. Any serious side effects warrant prompt medical help.

How Is Papaverine Administered for Different Medical Conditions?

The mode of administration depends on the condition being treated and the desired effect duration. For example, in coronary artery spasms or narrowing, cardiologists may inject papaverine directly into the coronary artery for rapid vessel dilation (sometimes for diagnostic purposes, such as FFR testing).

In acute situations, intravenous administration is common for fast action. For chronic circulation issues or spasms, oral forms may be prescribed for regular use. During surgery, papaverine may be applied topically to blood vessels (e.g., to the external surface of the internal mammary artery to prevent spasm during cardiac surgery).

In severe cerebral artery spasm (e.g., after subarachnoid hemorrhage), papaverine may be administered intrathecally (into the cerebrospinal fluid) or directly into the blood vessel. In short, papaverine can be targeted to the affected area as needed.

What Are the Potential Drug Interactions When Using Papaverine?

Those using multiple medications often wonder about drug interactions. Papaverine should be used cautiously with drugs affecting heart rhythm (especially those causing QT prolongation) or with substances like antihistamines or cocaine, which may affect heart electrical activity. Papaverine can alter blood pressure and heart rate, posing added risks for some patients.

Combined use with central nervous system depressants (such as strong sedatives) can enhance sedative effects. Alcohol can also increase papaverine’s potential side effects. Anyone taking regular medications or with chronic illnesses should consult a doctor or pharmacist before starting papaverine, so interactions can be managed or dosages adjusted.

Is Papaverine Used as an Antitumor Agent in Modern Medicine?

While cancer treatment is a rapidly evolving, multidisciplinary field, some research suggests papaverine may have effects on cancer cells beyond its spasmolytic and vasodilatory actions. In laboratory studies, papaverine has been shown to slow the growth of certain tumor cells or sensitize them to radiotherapy—particularly in hypoxic (low oxygen) tumors where it may act as a “radiosensitizer.”

In addition, studies on oncolytic virus therapies (viruses targeting cancer cells) indicate papaverine may enhance tumor delivery of these viruses by increasing blood flow. However, these findings are still largely experimental. Papaverine is not a routine cancer treatment but remains a topic of scientific interest for its potential roles.

What Precautions Should Be Taken Before Using Papaverine for Any Condition?

If you are considering or have been prescribed papaverine, your heart and circulatory health are especially important. Severe heart rhythm disturbances (e.g., high-grade AV block) may be worsened by papaverine. Those with glaucoma should also be careful, as changes in vessel and intraocular pressure can have unwanted effects.

Liver function should be monitored, as papaverine can rarely increase markers of liver injury. Its safety in pregnancy and breastfeeding has not been firmly established, so use in these situations should be avoided or closely monitored.

For ED treatment via injection, proper dosing and technique are crucial to avoid complications like priapism. Since dizziness or drowsiness can occur, avoid driving or operating machinery when starting papaverine.

Always inform your doctor of any other medications or supplements you use, as papaverine can interact unpredictably with many drugs. Dose adjustments or alternative medications may be necessary for safe, effective treatment.

Prof. Dr. Özgür KILIÇKESMEZ

Interventional Radiology and Neuroradiology Speaclist Prof. Dr. Özgür Kılıçkesmez graduated from Cerrahpaşa Medical Faculty in 1997. He completed his specialization at Istanbul Education and Research Hospital. He received training in interventional radiology and oncology in London. He founded the interventional radiology department at Istanbul Çam and Sakura City Hospital and became a professor in 2020. He holds many international awards and certificates, has over 150 scientific publications, and has been cited more than 1500 times. He is currently working at Medicana Ataköy Hospital.