Stereoselective Demethylation of the Enantiomers of Nefopam, an Experimental Antidepressant and Skeletal Muscle Relaxant

Bolt, A. G.; Graham, Gary; Wilson, P.

doi:10.3109/00498257409052111

Cited by 16 publications

(8 citation statements)

References 10 publications

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“…The impact in vivo of these differences is not known because there is no information on the relative plasma concentrations of the enantiomers or on their kinetics. In addition, early reports indicated differences in the rates of demethylation of the individual enantiomers to form (+) or (−)nornefopam, 5 thus suggesting potential differences in the pharmacokinetics of the respective parent enantiomers. Although the (+) and (−)desmethyl metabolites constitute major metabolic pathways that account for greater than 50% of the products found in human urine, their disposition kinetics have not been documented and it is not known whether these metabolites are present in plasma.…”

mentioning

confidence: 99%

Nefopam enantiomers: Preclinical pharmacology/toxicology and pharmacokinetic characteristics in healthy subjects after intravenous administration

et al. 2000

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mentioning

confidence: 99%

Nefopam enantiomers: Preclinical pharmacology/toxicology and pharmacokinetic characteristics in healthy subjects after intravenous administration

et al. 2000

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“…Third, we did not clarify the mechanism by which nefopam reduces the incidence of rocuronium-induced withdrawal response. Fourth, nefopam may influence the neuromuscular block because it was initially developed as a muscle relaxant, even though we did not experience any significantly delayed recovery from the neuromuscular block and postoperative residual block in this study [11,25,26]. Based on these limitations, further study is re quired to reveal whether nefopam has local or central effects on the pain control mechanism, whether it has synergistic or additional effects with opioids, and whether it may also influence the effect of neuromuscular blockers.…”

Section: Discussionmentioning

confidence: 74%

Combination of nefopam and remifentanil is more effective to reduce rocuronium-induced withdrawal response compared with remifentanil alone: a prospective, double-blinded, randomized control study

Jung

Kim

et al. 2018

Anesth Pain Med

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Rocuronium has generally been used in anesthetic practice by bolus injection for muscle relaxation during tracheal intubation or by continuous infusion [1]. However, rocuronium may induce a withdrawal response due to intense injection This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: We investigated the effect of combination of nefopam and remifentanil under the hypothesis that nefopam would effectively prevent rocuronium-induced withdrawal response by blocking serotonin receptors and providing a synergistic or additional effect with remifentanil.Methods: After receiving Institutional Review Board approval, 76 patients aged between 20 and 65 years with American Society of Anesthesiologists physical statuses of I or II were randomly allocated to the control group and nefopam group. In the control group, 102 ml of 0.9% sodium chloride solution was infused one hour before surgery at 100 ml/h. In the nefopam group, 20 mg nefopam (2 ml) in 100 ml of a 0.9% sodium chloride solution was infused one hour before surgery at 100 ml/h. Rocuronium (0.6 mg/kg) was injected after the induction of anesthesia with remifentanil and propofol at target concentrations of 2.0 ng/ml and 3.0 mg/ml, respectively. The grades of rocuronium-induced withdrawal response were evaluated using a four-point scale. The hemodynamics and respiratory rates were recorded upon operating room arrival, after anesthesia induction, and one minute post-injection of rocuronium.Results: Two patients (nefopam group) were excluded due to incomplete infusion and side effects; thus, 74 patients were finally analyzed. The overall incidence of rocuroniuminduced withdrawal response was significantly lower in nefopam group (27.8%, n = 36) than in control group (60.5%, n = 38) (P = 0.005). Conclusions:The combination of nefopam (20 mg) and remifentanil is more effective at reducing rocuronium-induced withdrawal response than remifentanil infusion alone with stable hemodynamics.

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“…Starting at this time, the paradigm of most studies about this newly renamed drug had shifted from a muscle relaxant [7,8] or an antidepressant [8,9] to an analgesic [10,11,12,13,14]. However, most of the studies have ignored NFP's role as an analgesic.…”

Section: Brief History Of Nefopammentioning

confidence: 99%

Rediscovery of Nefopam for the Treatment of Neuropathic Pain

Kim

Abdi

2014

Korean J Pain

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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.

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Stereoselective Demethylation of the Enantiomers of Nefopam, an Experimental Antidepressant and Skeletal Muscle Relaxant

Cited by 16 publications

References 10 publications

Nefopam enantiomers: Preclinical pharmacology/toxicology and pharmacokinetic characteristics in healthy subjects after intravenous administration

Nefopam enantiomers: Preclinical pharmacology/toxicology and pharmacokinetic characteristics in healthy subjects after intravenous administration

Combination of nefopam and remifentanil is more effective to reduce rocuronium-induced withdrawal response compared with remifentanil alone: a prospective, double-blinded, randomized control study

Rediscovery of Nefopam for the Treatment of Neuropathic Pain

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