Evidence of the involvement of dopamine in the analgesic effect of nefopam

Esposito, Ennio; Romandini, S.; Merlo‐Pich, Emilio; Mennini, Tiziana; Samanin, R.

doi:10.1016/0014-2999(86)90762-4

Cited by 44 publications

(26 citation statements)

References 19 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: 71%

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: 71%

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

et al. 2000

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“…In addition, the nefopam-induced blockade BIELLA ET AL. of central serotonin uptake (Esposito et al, 1986;Fasmer et al, 1987;Vonvoigtlander et al, 1983), a proper analgesic mechanism, is short-lived and incongruent with the prolonged period of post-operative analgesia. Finally, nefopam at 32 mg/kg ip slows brain serotonin degradation for only a few hours: the serotonin metabolite 5-hydroxyindolacetic acid, which is decreased at 2 h, is normal at four h (Chang et al, 1981;Fuller and Snoddy, 1993).…”

Section: Discussionmentioning

confidence: 98%

Neuronal Sensitization and Its Behavioral Correlates in a Rat Model of Neuropathy Are Prevented by a Cyclic Analog of Orphenadrine

Biella

Groppetti

Novelli

et al. 2003

Journal of Neurotrauma

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N-methyl-D-aspartic acid (NMDA) is an agonist at the homonymous receptor implicated in the development of neuronal sensitization and its behavioral correlates. An effective modulation of the NMDA effects, achieved also by uncompetitive antagonists, could contribute to controlling pain symptoms in several neuropathic syndromes. Because nefopam is a known analgesic derivative of orphenadrine and of its congener diphenhydramine, both uncompetitive NMDA receptor antagonists, we tested the effect of nefopam on the developing pain and neuronal anomalies in an animal model of chronic pain with NMDA receptor involvement. A single intraperitoneal injection of nefopam was administered twenty minutes prior to the chronic constriction injury of the sciatic nerve (CCI rats). In the first 10 days, nefopam (30 mg/kg) significantly decreased behavioral signs of neuropathic pain and the stimulus-evoked electrophysiological anomalies in recordings at 14 days, with only slight manifestation afterwards. The dose of 20 mg/kg was ineffective. Nefopam injected after constriction was ineffective. In normal non-operated rats, Nefopam had no effect on the electrophysiological and behavioral parameters. Iontophoretic nefopam (1 mM, 50-80 nA, positive current) in normal rats did not change the spontaneous neuronal activity, but reduced the mean response to noxious stimuli and the concurrent iontophoretic NMDA evoked activity. In CCI rats, iontophoretic nefopam did not significantly modify the spontaneous hyperactivity but reduced significantly both the frequency of the responses to noxious stimuli, and the duration of the afterdischarge. We propose that nefopam exerts a preventive analgesic effect, with a possible role in modulating NMDA receptor-mediated effects in central sensitization.

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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.…”

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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Evidence of the involvement of dopamine in the analgesic effect of nefopam

Cited by 44 publications

References 19 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

Neuronal Sensitization and Its Behavioral Correlates in a Rat Model of Neuropathy Are Prevented by a Cyclic Analog of Orphenadrine

Identifying mechanism-of-action targets for drugs and probes

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