Recent advances - Flupirtine Dr S. Parthasarathy MD DA DNB PhD FICA, Dip software based statistics

What is it ?? It is a nonopioid, non-NSAID analgesic,- aminopyridine Flupirtine acts indirectly as N-methyl-D-aspartate (NMDA) receptor antagonist by activation of K + channels. selective neuronal potassium channel openers (SNEPCO) Analgesic

Others Spinal polysynaptic reflex mediated by NMDA is blocked – so some muscle relaxation It has been found that flupirtine also antagonizes both glutamate and NMDA induced increase in intracellular levels of Ca ++, as observed in in vitro cultures of cortical and hippocampal neurons = no apoptosis - neuroprotection Possible antiparkinson effect

Pharmacokinetics After oral administration, peaks at 1.6 hours Metabolized in the liver and excreted predominantly in urine 18 % unchanged excretion in feces. Oral route – India 50 and 100 mg tablets But described rectal and intravenous

What is its use ?? Drug Controller General of India (DCGI) has approved flupirtine maleate 100 mg for treatment of acute and chronic pain, i.e., for painful increased muscle tone of the posture and motor muscles, primary headache, tumor pain, dysmenorrheal, and pain after trauma/orthopedic operations and injuries. from: %20FROM%2001.htm. %20FROM%2001.htm

Some standing examples – our professors Studies have shown that flupirtine reduced cancer pain more effectively than tramadol and pentazocine Flupirtine has been found to reduce the pain of fibromyalgia better than other available drugs. Flupirtine 380 mg/day was found to be effective in reducing lumbar and cervical spinal root pain in comparison with aspirin 1800 mg/day.

Postoperative pain 300 mg of flupirtine is comparable with 150 mg tramadol or 150 mg of diclofenac in the postoperative period. Studies in orthopedic surgeries, hysterectomies and episiotomies, it is comparable with diclo and pentazocine with less side effects

Side effects Transient faintness and dizziness pruritis (9%), dry mouth and gastric fullness (5%), nausea, and muscle tremor (2%). Other side effects were heart burn, vomiting, disturbed sleep, sedation, headache, fatigue, and mood elevation. Endoscopic ulcers with NSAIDs – nil with flupirtine 9 Vs 19 % vomiting incidence with flupirtine and tramadol

Less useful It lacks anti-inflammatory effect which limits its use in inflammatory conditions such as rheumatism, rheumatic fever, and osteoarthritis Yes it works but less efficient Children - ? But can be used in more than six years

Opioids ?? Long-term use of opioids for treatment of pain leads to constipation, nausea, sedation, confusion, pruritis, urinary retention, tolerance, and dependence. These adverse effects were not seen with flupirtine when given daily for 12 months in chronic pain. Transaminases estimation in long term use !!

Other benefits Its antiapoptotic, cytoprotective, and antioxidant properties can be used in treatment of neurodegenerative diseases. No effects on respiration, lack of tolerance, or physical dependence are added advantage over opioids Neuronal excitability decreased – fits, neuralgia, chronic pain states !!!

When not to give ?? Flupirtine is avoided in patients with history of hypersensitivity to flupirtine, hepatic encephalopathy, cholestasis, myasthenia gravis, chronic alcoholism, primary biliary cirrhosis, liver disease.

Summary Chemistry Mechanism Uses Advantages Contraindications Side effects

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