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The xerogenic potency and mechanism of action of tramadol inhibition of salivary secretion in rats.

Journal article
Authors Bengt Götrick
Gunnar Tobin
Published in Archives of oral biology
Volume 49
Issue 12
Pages 969-73
ISSN 0003-9969
Publication year 2004
Published at Institute of Physiology and Pharmacology, Dept of Pharmacology
Pages 969-73
Language en
Keywords Acetylcholine, administration & dosage, Adrenergic alpha-Antagonists, pharmacology, Adrenergic beta-Antagonists, pharmacology, Analgesics, Opioid, administration & dosage, Animals, Chelating Agents, pharmacology, Citric Acid, pharmacology, Dose-Response Relationship, Drug, Drug Interactions, Female, Injections, Intravenous, Phentolamine, pharmacology, Propranolol, pharmacology, Rats, Rats, Sprague-Dawley, Reflex, Salivation, drug effects, Tramadol, administration & dosage
Subject categories Pharmacology, Physiology


Tramadol is a centrally acting analgesic with weak opioid agonist properties, which also has monoaminergic activity, exerted via inhibition of neuronal uptake of serotonin and norepinephrine. Tramadol is generally well tolerated and the most common adverse events are nausea, dizziness, drowsiness, sweating, vomiting and dry mouth. Currently it was examined by which principal mechanism tramadol induces oral dryness. The effects of intravenous administration (+/-)-tramadol were studied in rats on the flow of saliva in response to a peripheral cholinergic stimulus or to reflex activation involving the relay of impulses in the central nervous system. In pentobarbitone-anaesthetized rats, the salivary secretion to acetylcholine (0.1-10 micromol/kg IV) was increased by up to 110% by tramadol (1-5 mg/kg IV) and the protein concentration therein by up to 400%. The administration alpha- and beta-adrenoceptor antagonists resulted in almost identical acetylcholine-evoked responses as in the absence of tramadol. The secretory response to the application of citric acid on the tongue of the rat was reduced by 38% and by 64%, respectively, at 5 and 10 mg/kg IV of tramadol (p < 0.05-0.01). Thus, tramadol exerts its principal xerogenic effect by activating inhibitory pathways in the central nervous system and has no anticholinergic effect on the salivary glands at dosages that may be clinically relevant. Furthermore, the tramadol-induced increase of the acetylcholine-evoked secretion occurred at a glandular level and depended most likely on a release of noradrenaline from glandular nerve terminals.

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