The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
The hypoalgesic effect of tramadol in relation to CYP2D6*
Abstract
Tramadol inhibits norepinephrine reuptake, stimulates serotonin release, and acts with mu-opioid receptors by way of its metabolite (+)-M1. Formation of M1 seems to depend on the genetic polymorphic CYP2D6. The analgesic effect of 2 mg/kg tramadol was evaluated in 15 extensive and 12 poor metabolizers of sparteine in two parallel, randomized, double-blind, placebo-controlled crossover studies that used experimental pain models. In extensive metabolizers, tramadol increased pressure pain detection (p = 0.03) and tolerance (p = 0.06) thresholds, as well as thresholds for eliciting nociceptive reflexes, after single (p = 0.0002) and repeated (p = 0.06) stimulation of the sural nerve. Peak pain and pain area in the cold pressor test were reduced (p = 0.0006 and 0.0009). In poor metabolizers, only thresholds to pressure pain tolerance (p = 0.02) and nociceptive reflexes after single stimulation (p = 0.04) were increased and the reflex threshold was less increased in poor metabolizers than in extensive metabolizers (p = 0.02). The serum concentration of (+)-M1 2 to 10 hours after tramadol ranged from 10 to 100 ng/L in extensive metabolizers, whereas in poor metabolizers serum concentrations of (+)-M1 were below or around the detection limit of 3 ng/ml. It is concluded that formation of (+)-M1 by way of CYP2D6 is important for the effect of tramadol on experimental pain.
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Metadata
- Authors
- Poulsen, L., Arendt-Nielsen, L., Brøsen, K., & Sindrup, S. H.
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 1996-12
- Volume
- 60
- Issue
- 6
- Pages
- 636-644
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W1965228291
- Cited by
- 386
- References
- 25
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- closed
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- Poulsen, L., Arendt-Nielsen, L., Brøsen, K., & Sindrup, S. H. (1996). The hypoalgesic effect of tramadol in relation to CYP2D6*. Clinical Pharmacology & Therapeutics. https://doi.org/10.1016/s0009-9236(96)90211-8
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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