Rediscovery of Nefopam for the Treatment of Neuropathic Pain
1
조회
0
다운로드
21
인용
0
참고문헌
키워드
초록
Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the non- sedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP’s mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15−20 min or with continuous infusion of 60−120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90−180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.
Abstract
Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the non- sedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP’s mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15−20 min or with continuous infusion of 60−120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90−180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.
참고문헌 (50)
- Gregori-Puigjané E, "Identifying mechanism-of-action targets for drugs and probes", Proc Natl Acad Sci U S A, 109, pp.11178~11183 (2012)
- Moore RA, "Single dose oral analgesics for acute postoperative pain in adults", Cochrane Database Syst Rev, (9), pp.CD008659~ (2011)
- Alfonsi P, "Nefopam, a nonsedative benzoxazocine analgesic, selectively reduces the shivering threshold in unanesthetized subjects", Anesthesiology, 100, pp.37~43 (2004)
- Heel RC, "Nefopam : a review of its pharmacological properties and therapeutic efficacy", Drugs, 19, pp.249~267 (1980)
- Podranski T, "Compartmental pharmacokinetics of nefopam during mild hypothermia", Br J Anaesth, 108, pp.784~791 (2012)
- Bassett JR, "Studies on the peripheral pharmacology of fenazoxine, a potential antidepressant drug", Br J Pharmacol, 37, pp.69~78 (1969)
- Tobin WE, "Nefopam hydrochloride: a novel muscle relaxant", J Clin Pharmacol New Drugs, 12, pp.230~238 (1972)
- Bolt AG, "Stereoselective demethylation of the enantiomers of nefopam, an experimental antidepressant and skeletal muscle relaxant", Xenobiotica, 4, pp.355~363 (1974)
- Koe BK, "Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain", J Pharmacol Exp Ther, 199, pp.649~661 (1976)
- Cohen A, "Nefopam hydrochloride for pain relief", Curr Ther Res Clin Exp, 16, pp.184~193 (1974)
- Klotz AL, "Long-term safety of Nefopam hydrochloride (Acupan), a new analgesic formulation", Curr Ther Res Clin Exp, 16, pp.602~608 (1974)
- Workmon FC, "A clinical evaluation of nefopam hydrochloride (Acupan): a new analgesic", Curr Ther Res Clin Exp, 16, pp.609~616 (1974)
- Kolodny AL, "Further clinical evaluations of nefopam hydrochloride, a new analgesic", Curr Ther Res Clin Exp, 17, pp.519~524 (1975)
- Kakkar M, "Single dose oral nefopam for acute postoperative pain in adults", Cochrane Database Syst Rev, (3), pp.CD007442~ (2009)
- Izzo V, "Action and effectiveness of nefopam chloride in the control of postoperative shivering", Minerva Anestesiol, 57, pp.760~762 (1991)
- Yeon A Kim, "Comparison of meperidine and nefopam for prevention of shivering during spinal anesthesia", Korean Journal of Anesthesiology, 64(3), pp.229~233 (2013), 대한마취통증의학회
- Park SM, "Efficacy spectrum of antishivering medications: meta-analysis of randomized controlled trials", Crit Care Med, 40, pp.3070~3082 (2012)
- Bilotta F, "Nefopam for severe hiccups", N Engl J Med, 343, pp.1973~1974 (2000)
- Bilotta F, "Nefopam for refractory postoperative hiccups", Anesth Analg, 93, pp.1358~1360 (2001)
- Pajot S, "Hiccup during weaning from mechanical ventilation : the use of nefopam", Br J Anaesth, 99, pp.748~749 (2007)
- Barrot M, "Tests and models of nociception and pain in rodents", Neuroscience, 211, pp.39~50 (2012)
- Jaggi AS, "Animal models of neuropathic pain", Fundam Clin Pharmacol, 25, pp.1~28 (2011)
- Hunskaar S, "The formalin test in mice: dissociation between inflammatory and non-inflammatory pain", Pain, 30, pp.103~114 (1987)
- 조수영, "Antinociceptive Effect of Intrathecal Nefopam and Interaction with Morphine in Formalin-Induced Pain of Rats", The Korean Journal of Pain, 26(1), pp.14~20 (2013), 대한통증학회
- Girard P, "Gillardin JM. Nefopam reduces thermal hypersensitivity in acute and postoperative pain models in the rat", Pharmacol Res, 44, pp.541~545 (2001)
- Buritova J, "Effects of nefopam on the spinal nociceptive processes : a c-Fos protein study in the rat", Eur J Pharmacol, 441, pp.67~74 (2002)
- Laboureyras E, "Long-term pain vulnerability after surgery in rats: prevention by nefopam, an analgesic with antihyperalgesic properties", Anesth Analg, 109, pp.623~631 (2009)
- Evans MS, "Nefopam for the prevention of postoperative pain : quantitative systematic review", Br J Anaesth, 101, pp.610~617 (2008)
- Tigerstedt I, "Comparison of the analgesic dose-effect relationships of nefopam and oxycodone in postoperative pain", Acta Anaesthesiol Scand, 23, pp.555~560 (1979)
- Dordoni PL, "Effect of ketorolac, ketoprofen and nefopam on platelet function", Anaesthesia, 49, pp.1046~1049 (1994)
- Gasser JC, "Respiratory effects of nefopam", Clin Pharmacol Ther, 18, pp.175~179 (1975)
- Guindon J, "Recent advances in the pharmacological management of pain", Drugs, 67, pp.2121~2133 (2007)
- Torres GE, "Plasma membrane monoamine transporters: structure, regulation and function", Nat Rev Neurosci, 4, pp.13~25 (2003)
- Max MB, "Bonica's management of pain", pp.1710~1726 (2001), Lippincott Williams & Wilkins
- Novelli A, "Nefopam inhibits calcium influx, cGMP formation, and NMDA receptor-dependent neurotoxicity following activation of voltage sensitive calcium channels", Amino Acids, 28, pp.183~191 (2005)
- Verleye M, "Nefopam blocks voltage-sensitive sodium channels and modulates glutamatergic transmission in rodents", Brain Res, 1013, pp.249~255 (2004)
- Biella GE, "Neuronal sensitization and its behavioral correlates in a rat model of neuropathy are prevented by a cyclic analog of orphenadrine", J Neurotrauma, 20, pp.593~601 (2003)
- Novelli A, "Nefopam is more potent than carbamazepine for neuroprotection against veratridine in vitro and has anticonvulsant properties against both electrical and chemical stimulation", Amino Acids, 32, pp.323~332 (2007)
- Czuczwar M, "Nefopam enhances the protective activity of antiepileptics against maximal electroshock-induced convulsions in mice", Pharmacol Rep, 63, pp.690~696 (2011)
- Löscher W, "New Horizons in the development of antiepileptic drugs: innovative strategies", Epilepsy Res, 69, pp.183~272 (2006)
- Hoebel BG, "Microdialysis studies of brain norepinephrine, serotonin, and dopamine release during ingestive behavior. Theoretical and clinical implications", Ann N Y Acad Sci, 575, pp.171~191 (1989)
- Hoyer D, "International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin)", Pharmacol Rev, 46, pp.157~203 (1994)
- Fink KB, "5-HT receptor regulation of neurotransmitter release", Pharmacol Rev, 59, pp.360~417 (2007)
- Barnes NM, "A review of central 5-HT receptors and their function", Neuropharmacology, 38, pp.1083~1152 (1999)
- Bannister K, "Preclinical and early clinical investigations related to monoaminergic pain modulation", Neurotherapeutics, 6, pp.703~712 (2009)
- Cotecchia S, "Protein-protein interactions at the adrenergic receptors", Curr Drug Targets, 13, pp.15~27 (2012)
- Girault JA, "The neurobiology of dopamine signaling", Arch Neurol, 61, pp.641~644 (2004)
- Benzon HT, "The neuropathic pain scales", Reg Anesth Pain Med, 30, pp.417~421 (2005)
- Mather GG, "Nefopam enantiomers: preclinical pharmacology", toxicology and pharmacokinetic characteristics in healthy subjects after intravenous administration, 2000, pp.12, 153~159
- Durrieu G, "Overview of adverse reactions to nefopam: an analysis of the French Pharmacovigilance database", Fundam Clin Pharmacol, 21, pp.555~558 (2007)