Evaluation of nefopam as a monoamine uptake inhibitor in vivo in mice

Fuller, Ray W.; Snoddy, Harold D.

doi:10.1016/0028-3908(93)90064-a

Cited by 70 publications

(38 citation statements)

References 12 publications

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“…The binding affinities of NEF enantiomers for the opiate receptors µ, ␦, , (Ն10 µM) is similar to that observed for (±)NEF by Tresnak-Rustad and Wood 17 (26 µM). The potent inhibition of synaptosomal uptake of dopamine, norepinephrine, and serotonin reported previously, 4,[17][18][19] combined with binding to the serotonin receptor 5HT2 reported here, provide a possible explanation for the analgesic activity of NEF without respiratory depression.…”

Section: Comparative Receptologymentioning

confidence: 68%

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

et al. 2000

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Section: Comparative Receptologymentioning

confidence: 68%

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

et al. 2000

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“…Whereas phenotypic patterns in animal models have suggested activities via the serotonin, glutamate, and dopamine circuits (25)(26)(27)(28), these suggestions and experiments were made and undertaken before direct assays were available, except as in brain homogenates. For instance, though evidence from classical pharmacology supports a role for the monoamine transporters in nefopam's activity (25,29), molecular binding affinities and selectivities remain unknown. Whereas chemoinformatic inference finds little similarity to glutaminergic ligands, SEA does predict serotonergic activity (E-value ¼ 1.40 × 10 −26 ).…”

Section: Resultsmentioning

confidence: 99%

Identifying mechanism-of-action targets for drugs and probes

Gregori‐Puigjané

Setola

Hert

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

165

141

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Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action. Using a chemoinformatics approach, we sought to "de-orphanize" drugs that lack primary targets. Surprisingly, targets could be easily predicted for many: Whereas these targets were not known to us nor to the common databases, most could be confirmed by literature search, leaving only 13 Food and Drug Administration-approved drugs with unknown targets; the number of drugs without molecular targets likely is far fewer than reported. The number of worldwide drugs without reasonable molecular targets similarly dropped, from 352 (25%) to 44 (4%). Nevertheless, there remained at least seven drugs for which reasonable mechanism-of-action targets were unknown but could be predicted, including the antitussives clemastine, cloperastine, and nepinalone; the antiemetic benzquinamide; the muscle relaxant cyclobenzaprine; the analgesic nefopam; and the immunomodulator lobenzarit. For each, predicted targets were confirmed experimentally, with affinities within their physiological concentration ranges. Turning this question on its head, we next asked which drugs were specific enough to act as chemical probes. Over 100 drugs met the standard criteria for probes, and 40 did so by more stringent criteria. A chemical information approach to drug-target association can guide therapeutic development and reveal applications to probe biology, a focus of much current interest. chemical tools | drug target identification | polypharmacology

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“…Equally important, fewer patients in the ................................................................................................................................................................................................................... nefopam group than in the other groups required vasoactive drugs for optimal control of cerebral perfusion pressure. Although the mechanisms underlying the analgesic action of nefopam are unclear, the drug does not bind to opiate receptors, but inhibits synaptic uptake of several neurotransmitters, including dopamine, norepinephrine and serotonin [19,20]. Ample evidence confirms the efficacy of nefopam for the treatment [2] and prevention [4][5][6] of postanaesthetic shivering.…”

Section: Discussionmentioning

confidence: 99%

Nefopam or clonidine in the pharmacologic prevention of shivering in patients undergoing conscious sedation for interventional neuroradiology

Bilotta¹,

Ferri²,

Giovannini³

et al. 2005

Anaesthesia

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SummaryThe aim of this randomised, double-blind study was to investigate the usefulness of intravenous nefopam, clonidine or placebo in preventing shivering in patients undergoing conscious sedation for interventional neuroradiological procedures. A total of 101 patients were prospectively enrolled and assigned to one of three groups to receive nefopam, clonidine or placebo. The overall incidence of intra-operative shivering was significantly lower in patients treated with nefopam than in those treated with clonidine or placebo (2 ⁄ 32 (6%) vs. 11 ⁄ 38 (29%), p < 0.02; 2 ⁄ 32 (6%) vs. 24 ⁄ 31 (77%), p < 0.0001, respectively). The number of patients who required ephedrine infusions to maintain a mean arterial pressure of 100 mm Hg was higher in the clonidine group than in the nefopam and placebo groups (18 ⁄ 38 (47%) vs. 5 ⁄ 32 (17%), p < 0.05; 18 ⁄ 38 (47%) vs. 6 ⁄ 31 (19%), p < 0.05, respectively). We found that both nefopam and clonidine significantly lowered the rate and severity of shivering during interventional neuroradiological procedures. Fewer patients in the nefopam group than in the other two groups required vasoactive drugs.

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Evaluation of nefopam as a monoamine uptake inhibitor in vivo in mice

Cited by 70 publications

References 12 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

Identifying mechanism-of-action targets for drugs and probes

Nefopam or clonidine in the pharmacologic prevention of shivering in patients undergoing conscious sedation for interventional neuroradiology

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