Long-term Use of Flupirtine Leads to Withdrawal Symptoms and is Associated with Dependency

Abstract

This is the case of a 44-year-old woman, who was treated as an inpatient because of withdrawal symptoms like sweating, tremors, sleeping disorders and irritability after long-term use of flupirtine. She recovered by symptom-based application of pipamperone within 72 h after flupirtine cessation.

Key words

flupirtine - N-methyl-D-aspartate receptor antagonist - withdrawal symptoms - dependency - addictive potential

• References

• 1 Devulder J. Flupirtine in pain management: pharmacological properties and clinical use. CNS Drugs 2010; 24: 867-881
• 2 Hummel T, Friedmann T, Pauli E et al. Dose-related analgesic effects of flupirtine. Br J Clin Pharmacol 1991; 32: 69-76
• 3 Kornhuber J, Bleich S, Wiltfang J et al. Flupirtine shows functional NMDA receptor antagonism by enhancing Mg²⁺ block via activation of voltage independent potassium channels. J Neural Transm 1999; 106: 857-867
• 4 Herrmann WM, Kern U, Aigner M. On the adverse reactions and efficacy of long-term treatment with flupirtine: preliminary results of an ongoing twelve-month study with 200 patients suffering from chronic pain states in arthrosis or arthritis. Postgrad Med J 1987; 63 (Suppl. 03) 87-103
• 5 Preston KL, Funderburk FR, Liebson IA et al. Evaluation of the abuse potential of the novel analgesic flupirtine maleate. Drug Alcohol Depend 1991; 27: 101-113
• 6 Nickel B, Borbe HO, Szelenyi I. Investigations with the novel non-opioid analgesic flupirtine in regard to possible benzodiazepine-like abuse inducing potential. Arzneimittelforschung 1990; 40: 905-908
• 7 Schep LJ, Knudsen K, Slaughter RJ et al. The clinical toxicology of γ-hydroxybutyrate, γ-butyrolactone and 1,4-butanediol. Clin Toxicol (Phila) 2012; 50: 458-470
• 8 Wetterling T, Kanitz RD, Besters B et al. A new rating scale for the assessment of the alcohol-withdrawal syndrome (AWS scale). Alcohol Alcohol 1997; 32: 753-760
• 9 Jakob R, Krieglstein J. Influence of flupirtine on a G-protein coupled inwardly rectifying potassium current in hippocampal neurones. Br J Pharmacol 1997; 122: 1333-1338
• 10 Gribkoff VK. The therapeutic potential of neuronal KCNQ channel modulators. Expert Opin Ther Targets 2003; 7: 737-748
• 11 Korsgaard MP, Hartz BP, Brown WD et al. Anxiolytic effects of Maxipost (BMS-204352) and retigabine via activation of neuronal Kv7 channels. J Pharmacol Exp Ther 2005; 314: 282-292
• 12 Brown DA, Passmore GM. Neural KCNQ (Kv7) channels. Br J Pharmacol 2009; 156: 1185-1195
• 13 Miceli F, Soldovieri MV, Martire M et al. Molecular pharmacology and therapeutic potential of neuronal Kv7-modulating drugs. Curr Opin Pharmacol 2008; 8: 65-74
• 14 Stoessel C, Heberlein A, Hillemacher T et al. Positive reinforcing effects of flupirtine – two case reports. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 1120-1121
• 15 Hansen HH, Waroux O, Seutin V et al. Kv7 channels: interaction with dopaminergic and serotonergic neurotransmission in the CNS. J Physiol 2008; 586: 1823-1832
• 16 Lodge NJ, Li YW. Ion channels as potential targets for the treatment of depression. Curr Opin Drug Discov Devel 2008; 11: 633-641
• 17 Trist DG. Excitatory amino acid agonists and antagonists: pharmacology and therapeutic applications. Pharm Acta Helv 2000; 74: 221-229
• 18 Ma YY, Cepeda C, Cui CL. The role of striatal NMDA receptors in drug addiction. Int Rev Neurobiol 2009; 89: 131-146