| http://linked.open...generalReferences
| - # Dayer P, Desmeules J, Collart L: [Pharmacology of tramadol] Drugs. 1997;53 Suppl 2:18-24. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/9190321 # Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, Donofrio P, Cornblath D, Sachdeo R, Siu CO, Kamin M: Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology. 1998 Jun;50(6):1842-6. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/9633738 # Harati Y, Gooch C, Swenson M, Edelman SV, Greene D, Raskin P, Donofrio P, Cornblath D, Olson WH, Kamin M: Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy. J Diabetes Complications. 2000 Mar-Apr;14(2):65-70. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/10959067 # Gobel H, Stadler T: [Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine] Drugs. 1997;53 Suppl 2:34-9. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/9190323 # Boureau F, Legallicier P, Kabir-Ahmadi M: Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Pain. 2003 Jul;104(1-2):323-31. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/12855342 # FDA label (en)
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| http://linked.open...mechanismOfAction
| - Tramadol and its O-desmethyl metabolite (M1) are selective, weak OP3-receptor agonists. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. The analgesic properties of Tramadol can be attributed to norepinephrine and serotonin reuptake blockade in the CNS, which inhibits pain transmission in the spinal cord. The (+) enantiomer has higher affinity for the OP3 receptor and preferentially inhibits serotonin uptake and enhances serotonin release. The (-) enantiomer preferentially inhibits norepinephrine reuptake by stimulating alpha(2)-adrenergic receptors. (en)
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