Ibudilast (development codes: AV-411 or MN-166) is an

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

drug used mainly in Japan, which acts as a

phosphodiesterase inhibitor A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cycl ...

, inhibiting the PDE4 subtype to the greatest extent, but also showing significant inhibition of other PDE subtypes.

Medical uses

Japan Japan is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...

, ibudilast oral capsules are approved for the treatment of

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

, and for improvement of

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

secondary to chronic cerebral circulation impairment associated with sequelae of

cerebral infarction Cerebral infarction, also known as an ischemic stroke, is the pathologic process that results in an area of necrotic tissue in the brain (cerebral infarct). In mid to high income countries, a stroke is the main reason for disability among peo ...

. Ibudilast ophthalmic solution is indicated for the treatment of

allergic conjunctivitis Allergic conjunctivitis (AC) is Allergic Inflammation, inflammation of the conjunctiva (the membrane covering the white part of the eye) due to allergy. Although allergens differ among patients, the most common cause is hay fever. Symptoms consist ...

and

hay fever Allergic rhinitis, of which the seasonal type is called hay fever, is a type of rhinitis, inflammation in the nose that occurs when the immune system overreacts to allergens in the air. It is classified as a Allergy, type I hypersensitivity re ...

. It may have some use reducing methamphetamine, opioid, and alcohol addiction.

Pharmacology

Ibudilast has

bronchodilator A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lun ...

vasodilator Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wal ...

and neuroprotective effects, and is mainly used in the treatment of

and

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

. It inhibits

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

aggregation, and may also be useful in the treatment of

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

. Ibudilast crosses the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

and suppresses

glial cell Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...

activation. This activity has been shown to make ibudilast useful in the treatment of

neuropathic pain Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuo ...

and it not only enhances

analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...

produced by

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

drugs, but also reduces the development of tolerance.

Pharmacodynamics

Ibudilast is principally a PDE4 inhibitor, but it also has significant affinity for PDE3, PDE10A, PDE11. Ibudilast has also been shown to act as an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.toll-like receptor Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane protein, single-spanning receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophages ...

4 ( TLR4). This likely plays a large part in its effect, specifically its synergy with opioid drugs, its

effect, and its own painkilling effect. It is unknown if the PDE4-inhibiting properties potentiate the effects of TLR4 inactivation and/or vice versa, despite that some of their effects are shared, such as

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

reducing properties. TLR4 antagonists theoretically reverse the increase in pain and inflammation caused by most TLR4

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s, which includes alcohol & many

opiate An opiate is an alkaloid substance derived from opium (or poppy straw). It differs from the similar term ''opioid'' in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain ( ...

drugs.

References

{{Phosphodiesterase inhibitors Pyrazolopyridines PDE4 inhibitors