Flupirtine as a Potential Treatment for Fibromyalgia

Abstract

exhibits indirect N-methyl-D-aspartate (NMDA) receptor antagonism via activation of potassium channels, leading to the suppression of neuronal overex-citability. 3,4 Thus, flupirtine has been used as an analgesic for the last 35 years in the management of pain and also exerts skeletal muscle relaxation and neuroprotection properties. 3–5 Flupirtine is available as the maleate salt, a hydrophilic compound that is rap-idly absorbed from the gastrointestinal tract with a bioavailability of 90%. 6,7 The volume of distribution (Vd) of 100 mg of flupirtine is 154 L in healthy volunteers and is up to 84% bound to human albumin. 6,7 The half-life of flupirtine depends on the route of administration, but is typically between 6.5–10.7 h. Following oral administration of 100 mg of flupirtine, clearance is 275 ml/min in healthy volunteers. 6,7 Flupirtine is metabolized in the liver by per-Flupirtine Abstract Fibromyalgia is a complex disorder characterised by chronic pain, fatigue, sleep disturbance and cognitive dys-function with limited benefit gained with current therapies. The mean global prevalence of 2.7% is estimated for this chronic condition. Pharmacological and non-pharmacological therapeutic approaches are often required as treatments of the challenges associated with fibromyalgia. Flupirtine, a non-opioid drug, exhibits effective analgesia in a range of acute and persistent pain conditions, and evidence as treatment of fibromyalgia is considered. Activation of Kv7 potassium channels and agonism at gamma-aminobutyric acid receptor A leading to indirect N-methyl-D-aspartate receptor antagonism is responsible for the analgesic effects of flupirtine and appears to be involved in other symptoms associated with fibromyalgia. Patients with fibromyalgia reported improved control of their symptoms without significant adverse effects in an observational audit in clinical practice. This article presents evidence that flupirtine, or related drugs, is a therapeutic option for the treatment of fibromyalgia. The pharmacology of flupirtine and mechanisms of action involved provide a spectrum of effects that would not only control the chronic pain characteristic of fibromyalgia but many of the other symptoms. Thus, further investigation of the efficacy of flupirtine or related drugs exhibiting a similar pharmacology as a treatment of fibromyalgia would be of interest. oxidase enzymes to the active N-acetylated analogue D13223 and 4-fluorohippuric, which are further oxidised and then conjugated inactive metabolites.