Flupirtine is an

aminopyridine Aminopyridine may refer to any of several chemical compounds: * 2-Aminopyridine * 3-Aminopyridine 3-Aminopyridine is an aminopyridine. It is a colorless solid. Preparation 3-Aminopyridine is prepared by heating nicotinamide with sodium hypobr ...

that functions as a centrally acting non-

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

analgesic that was originally used as an analgesic for acute and chronic pain but in 2013 due to issues with liver toxicity, the European Medicines Agency restricted its use to acute pain, for no more than two weeks, and only for people who cannot use other painkillers. In March 2018, marketing authorisations for flupirtine were withdrawn following a European Medicines Agency recommendation based on the finding that the restrictions introduced in 2013 had not been sufficiently followed in clinical practice, and cases of serious liver injury still occurred including liver failure. Flupirtine is a selective neuronal

potassium channel opener A potassium channel opener is a type of drug which facilitates ion transmission through potassium channels. Examples Some examples include: *Diazoxide vasodilator used for hypertension, smooth muscle relaxing activity *Minoxidil vasodilator u ...

(SNEPCO) that also has

NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

and GABAA receptor modulatory properties. It first became available in Europe in 1984 under the brand name Katadolon and after it went off patent many generic brands were introduced.

Uses

Flupirtine is used as an analgesic for acute pain, in moderate-to-severe cases. Its muscle relaxant properties make it popular for back pain and other

orthopaedic Orthopedic surgery or orthopedics ( alternatively spelt orthopaedics), is the branch of surgery concerned with conditions involving the musculoskeletal system. Orthopedic surgeons use both surgical and nonsurgical means to treat musculoskeletal ...

uses, but it is also used for migraines, in

oncology Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''� ...

, postoperative care, and gynaecology. In 2013 due to issues with liver toxicity, the European Medicines Agency restricted its use to acute pain, for no more than two weeks, and only for people who cannot use other painkillers.

Side effects

The most serious side effect is frequent

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fr ...

which prompted regulatory agencies to issue several warnings and restrictions. Flupirtine is devoid of negative psychological or motor function effects, or effects on reproductive function.

Abuse and dependence

Although some studies have reported flupirtine has no addictive properties, there was suggestion that it may possess some abuse potential and liability. There were at least two registered cases of flupirtine abuse. Drug tolerance does not develop in most cases, but has individually occurred.

Mechanism of action

Flupirtine is a selective neuronal

that also has indirect

and GABAA receptor modulatory properties.

History

Flupirtine was discovered and developed between the 1970s and the 1990s by Chemiewerk Homburg in

Frankfurt am Main Frankfurt, officially Frankfurt am Main (; Hessian: , "Frank ford on the Main"), is the most populous city in the German state of Hesse. Its 791,000 inhabitants as of 2022 make it the fifth-most populous city in Germany. Located on its na ...

, Germany, which became Degussa Pharma Group and then through mergers, ASTA Pharma and Asta Medica.

Retigabine Retigabine ( INN) or ezogabine (USAN) is an anticonvulsant used as an adjunctive treatment for partial epilepsies in treatment-experienced adult patients. The drug was developed by Valeant Pharmaceuticals and GlaxoSmithKline. It was approved by t ...

, in which the pyridine group in flupirtine is replaced with a phenyl group, was discovered as part of the same program and has a similar mechanism of action. It was approved for the treatment of pain in 1984 in Europe under the brand name Katadolon. As of 2013 it was used in 11 member countries: Bulgaria, Estonia, Germany, Hungary, Italy, Latvia, Lithuania, Poland, Portugal, Romania and Slovak Republic. Many generics entered the European market around 2011. It was never introduced to the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

market for any indication but in 2008, Adeona Pharmaceuticals, Inc. (now called Synthetic Biologics, Inc.) obtained an option to license issued and

patent pending "Patent pending" (sometimes abbreviated by "pat. pend." or "pat. pending") or "patent applied for" are legal designations or expressions that can be used in relation to a product or process once a patent application for the product or process ...

applications relating to flupirtine's use in the treatment of ophthalmic indications, particularly

retinitis pigmentosa Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...

. In 2010 retigabine was approved by the FDA as an anticonvulsant for the treatment of refractory partial-onset seizures in treatment-experienced patients. As of 2016 it is marketed under many brand names, including Efiret, Flupigil, Flupirtin, Flupirtina, Flupirtine, Flupizen, Fluproxy, Katadolon, Metanor, Trancolong, and Zentiva.Flupirtine
Drugs.com. Accessed 30 August 2016

Research

Flupirtine has been noted for its neuroprotective properties, and has been investigated for possible use in

Creutzfeldt–Jakob disease Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes ...

, Alzheimer's disease, and multiple sclerosis. It has also been proposed as a possible treatment for Batten disease. Flupirtine underwent a

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

as a treatment for multiple sclerosisFlupirtine as Oral Treatment in Multiple Sclerosis (FLORIMS)
Clinical Trials.gov Accessed 20 September 2011. and fibromyalgia.Pipex Pharmaceuticals (PPXP)' Oral Flupirtine Receives IND With FDA for Phase II Clinical Trial for Fibromyalgia
4/21/2008 Flupirtine showed promise for fibromyalgia due to its different action than the three approved by U.S.

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

drugs:

pregabalin Pregabalin, sold under the brand name Lyrica among others, is an anticonvulsant, analgesic and anxiolytic medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal and generalized anxiety diso ...

milnacipran Milnacipran (trade names Ixel, Savella, Dalcipran, Toledomin) is a serotonin–norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia. It is not approved for the clinical treatment of major depressive disorder in ...

, and

duloxetine Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth. It is a seroton ...

. Additionally, there are case reports regarding flupirtine as a treatment for fibromyalgia.Stoll AL, Belmont MA. (2000)
Fibromyalgia Symptoms Relieved by Flupirtine: An Open-Label Case Series
" ''Psychosomatics'' 41:371-372. Accessed 20 September 2011. Adeona Pharmaceuticals (now called Synthetic Biologics) sub-licensed its patents for using flupirtine for fibromyalgia to

Meda AB Meda AB is a specialty pharmaceutical company, headquartered in Solna, Sweden. Meda imports and markets pharmaceuticals, nutritional, and health-care products, and offers services including clinical research, registration, and logistics. At the ...

in May 2010.

References

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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...

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