Summary: An opioid analgesic used similarly to MORPHINE in the control of moderate to severe pain. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1097)

Top Publications

  1. Flöter T, Brunnmüller U. [Tilidine/naloxon retard in long-term administration in chronic pain and multimorbidity. Multicenter study of long-term tolerance and effectiveness in 2 years observation]. Fortschr Med Orig. 2002;120:29-35 pubmed
    ..years) with chronic pain and multimorbidity have been included in a multi-center 2-years' study with slow release Tilidine/Naloxone for efficacy and safety which included detailed laboratory examinations...
  2. Brennscheidt U, Brunnmüller U, Proppe D, Thomann P, Seiler K. Pharmacokinetics of tilidine and naloxone in patients with severe hepatic impairment. Arzneimittelforschung. 2007;57:106-11 pubmed
    The objective of the present study was to evaluate the pharmacokinetics of tilidine (CAS 20380-58-9), naloxone (CAS 465-65-6) and tilidine metabolites after administration of a single oral dose of a solution containing 100 mg tilidine ..
  3. Kohler C, Grobosch T, Binscheck T. Rapid quantification of tilidine, nortilidine, and bisnortilidine in urine by automated online SPE-LC-MS/MS. Anal Bioanal Chem. 2011;400:17-23 pubmed publisher
    The opioid tilidine is a prodrug which is hepatically metabolized to active nortilidine and bisnortilidine...
  4. Wörz R. [Chronic non-malignant pain. Opioids are also suitable for long-term treatment]. MMW Fortschr Med. 2006;148:47 pubmed
  5. Wehrmann T, Rausch D, Seiler K, Brennscheidt U, Caspary W. Tilidine does not affect human sphincter of Oddi motility--a randomized, controlled study. Aliment Pharmacol Ther. 1997;11:987-92 pubmed
    To investigate the effects of intravenous pentazocine and tilidine on sphincter of Oddi motility. Twenty patients with suspected sphincter of Oddi dysfunction were enrolled in a prospective, double-blind study...
  6. Wustrow I, Riedel K, Mikus G, Weiss J. In vitro identification of the cytochrome P450 isozymes involved in the N-demethylation of the active opioid metabolite nortilidine to bisnortilidine. Naunyn Schmiedebergs Arch Pharmacol. 2012;385:633-9 pubmed publisher
    b>Tilidine exhibits the highest consumption of opioids in Germany. The prodrug is hepatically metabolised in a sequential N-demethylation reaction...
  7. Regenthal R, Kruger M, Richter M, Preiss R. Poisoning with tilidine and naloxone: toxicokinetic and clinical observations. Hum Exp Toxicol. 1998;17:593-7 pubmed
    The opioid analgesic tilidine and its metabolites were detected by high performance liquid chromatography (HPLC) with UV-detection in serum from a 28 year-old woman who ingested 100 ml Valoron (o)N containing 6...
  8. Seiler K, Jahnchen E, Trenk D, Brennscheidt U, Heintz B. Pharmacokinetics of tilidine in terminal renal failure. J Clin Pharmacol. 2001;41:79-84 pubmed
    The aim of the present study was to investigate the pharmacokinetics of tilidine and its metabolites during the dialysis procedure and in the dialysis-free interval...
  9. Hogger P. Adverse effects of opioid analgesic treatment are correlated with a significant elevation in plasma epinephrine in healthy humans. Eur J Clin Pharmacol. 2000;56:463-8 pubmed
    ..and during painful electrical tooth-pulp stimulation under medication using the highly potent opioid analgesic tilidine in a fixed tilidine/naloxone combination and with the non-steroidal anti-inflammatory agent bromfenac...

More Information


  1. Verplaetse R, Tytgat J. Development and validation of a sensitive UPLC-MS/MS method for the analysis of narcotic analgesics in urine and whole blood in forensic context. Forensic Sci Int. 2012;215:136-45 pubmed publisher
    ..metabolites (buprenorphine, O-desmethyltramadol, fentanyl, norbuprenorphine, norfentanyl, pethidine, piritramide, tilidine and tramadol) in urine and whole blood...
  2. Fudala P, Johnson R. Development of opioid formulations with limited diversion and abuse potential. Drug Alcohol Depend. 2006;83 Suppl 1:S40-7 pubmed
  3. Nolte T. [The chronic pain patient: assuring long-term success]. Krankenpfl J. 2005;43:203 pubmed
  4. Cegla T, Walter F, Borchers A, Trenz M. [Postoperative pain therapy with tilidin and tilidin retard as an oral patient-controlled analgesia after uncomplicated myocardial revascularization]. Schmerz. 2003;17:110-6 pubmed
    ..The combination of sustained release with immediate release drugs as a patient controlled analgesia provides suitable and comfortable analgesia after myocardial bypass surgery. ..
  5. Tings T, Trenkwalder C. [When L-Dopa preparations, dopamine agonists or opioids? Therapy of restless legs syndrome]. MMW Fortschr Med. 2003;145:48-9 pubmed
  6. Hajda J, Jähnchen E, Oie S, Trenk D. Sequential first-pass metabolism of nortilidine: the active metabolite of the synthetic opioid drug tilidine. J Clin Pharmacol. 2002;42:1257-61 pubmed
    The disposition of nortildine, the active metabolite of the synthetic opioid drug tilidine, was investigated in healthy volunteers in a randomized, single-dose, three-way crossover design...
  7. Freye E, Latasch L. Effects of tramadol and tilidine/naloxone on oral-caecal transit and pupillary light reflex. Arzneimittelforschung. 2000;50:24-30 pubmed
    As has been demonstrated in binding studies the two opioids tilidine (CAS 27107-79-7)/naloxone (CAS 357-08-4) and tramadol (CAS 36282-47-0) differ in regard to their affinities to the opioid receptor site...
  8. Scharnagel R, Kaiser U, Schutze A, Heineck R, Gossrau G, Sabatowski R. [Chronic non-cancer-related pain. Long-term treatment with rapid-release and short-acting opioids in the context of misuse and dependency]. Schmerz. 2013;27:7-19 pubmed publisher
    ..Particular emphasis is placed on the administration of rapid-release and short-acting opioid preparations, which we consider to be particularly problematic. ..
  9. Hogger P, Rohdewald P. Comparison of tilidine/naloxone, tramadol and bromfenac in experimental pain: a double-blind randomized crossover study in healthy human volunteers. Int J Clin Pharmacol Ther. 1999;37:377-85 pubmed
    The analgesic efficacy and safety of single oral doses of two centrally acting compounds, the combination of 50 mg tilidine and 4 mg naloxone (Valoron N) and 50 mg tramadol (Tramal), were compared to 25, 50 and 75 mg of the non-steroidal ..
  10. Schutter U, Ritzdorf I, Heckes B. [The transdermal 7-day buprenorphine patch--an effective and safe treatment option, if tramadol or tilidate/naloxone is insufficient. Results of a non-interventional study]. MMW Fortschr Med. 2010;152 Suppl 2:62-9 pubmed
    ..The user-friendly 7-day application interval contributes to improving compliance and a reducing exposure to tablets. ..
  11. Zhang C, Zhang R, Na N, Delanghe J, Ouyang J. Direct monitoring changes of salbutamol concentration in serum by chemiluminescent imaging. J Chromatogr B Analyt Technol Biomed Life Sci. 2011;879:2089-94 pubmed publisher
    ..It provided us with excellent reference information for the individual dosage regimen of different Hp groups, which hopefully could become a potential method for further pharmaceutical research. ..
  12. Wörz R, Wörz E. [Long-term treatment of chronic pain with tilidine-naloxone. An analysis of 50 patients with chronic pain conditions of non-malignant origin]. Fortschr Med. 1995;113:388-92 pubmed
    ..chronic pain states were treated for a period of between six months and 14 years (median: 31 months) with tilidine-naloxone, and the results of tumor recorded. Amelioration of pain was achieved in an average of 60...
  13. Hoffmeister F. A comparison of the stimulus effects of codeine in rhesus monkeys under the contingencies of a two lever discrimination task and a cross self-administration paradigm: tests of generalization to pentazocine, buprenorphine, tilidine, and different dose. Psychopharmacology (Berl). 1988;94:315-20 pubmed
    ..Codeine-trained monkeys did not generalize to tilidine. These results indicate that monkeys do not behave in a qualitatively different way when presented with the study ..
  14. Vollmer K, Thomann P, Hengy H. Pharmacokinetics of tilidine and metabolites in man. Arzneimittelforschung. 1989;39:1283-8 pubmed
    b>Tilidine is a prodrug from which the active metabolite nortilidine is formed by demethylation...
  15. Junker U, Sarnow E, Tilke C. [Tilidine-Naloxone sustained-release tablets for chronic pain associated with musculoskeletal disease]. MMW Fortschr Med. 2006;148:45 pubmed
  16. Nosál ová G, Strapkova A, Korpas J. Relationship between the antitussic and analgesic activity of substances. Acta Physiol Hung. 1991;77:173-8 pubmed
    ..The antitussic effect of codeine, tilidine, tramadol and pentazocine has been studied in nonanesthetized healthy cats...
  17. Van Cauwenberge H, Ruhwiedel M, Albert A, Franchimont P. Comparative study of tilidine-naloxone and pentazocine in knee and hip osteoarthritis. Int J Clin Pharmacol Res. 1992;12:1-9 pubmed
    ..knee osteoarthritis and twenty-five from acute hip osteoarthritis, received pentazocine or a new preparation of tilidine-naloxone for a period of 2 weeks, in a double-blind study...
  18. Radbruch L, Glaeske G, Grond S, Münchberg F, Scherbaum N, Storz E, et al. Topical review on the abuse and misuse potential of tramadol and tilidine in Germany. Subst Abus. 2013;34:313-20 pubmed publisher
    Tramadol and tilidine (in combination with naloxone) are used as weak opioid analgesics in Germany. Tramadol is not scheduled in the German Narcotic Drugs Act...
  19. Maier C, Leclerc Springer J. [Life-threatening fentanyl and propofol addiction: interview with a survivor]. Anaesthesist. 2012;61:601-7 pubmed publisher
    ..presents an interview with a formerly addicted female anesthesiologist who after long-term abuse with oral tilidine combined with naloxone switched to intravenous administration of fentanyl and later on propofol...
  20. Thierauf A, Dettmeyer R, Wollersen H, Madea B. Aplastic right coronary artery and left coronary artery with a separate origin of the circumflex branch in a 31-year-old woman. Forensic Sci Int. 2007;173:178-81 pubmed
    ..The autopsy findings and the results of the toxicological examinations are presented and discussed in view of the cause of death. ..
  21. Hankemeier U, Herberhold D, Graff J. [Analgesia using oral administration of tilidine naloxone for extracorporeal shockwave lithotripsy. A double blind study]. Anasthesiol Intensivmed Notfallmed Schmerzther. 1991;26:143-7 pubmed
    ..of the anti-anxiety drug dipotassium clorazepate on the evening before ESWL together with the analgesic tilidine-naloxone before treatment was tested in a randomised double-blind study in 120 patients...
  22. Dobrila Z, Ljiljana S, Ljiljana Z. Spectrophotometric determination of tilidine using bromocresol green and bromophenol blue. Acta Pharm Hung. 1990;60:179-81 pubmed
    A spectrophotometric method is described for the determination of tilidine in its dosage forms (injection, drops, suppositories). The method is based on ion-pair extraction with chloroform at pH 3...
  23. Brunnmüller U. [Postoperative pain therapy in an accident surgery ward]. Unfallchirurg. 2003;106:443; author reply 444 pubmed
  24. Bolze S, Boulieu R. HPLC determination of ketamine, norketamine, and dehydronorketamine in plasma with a high-purity reversed-phase sorbent. Clin Chem. 1998;44:560-4 pubmed
    ..7% to 5.8% and 3.1% to 10.2% for all compounds respectively. The method is sensitive enough for monitoring ketamine, NK, and dehydroketamine in plasma during pharmacokinetic studies after an intravenous bolus of a low dose of ketamine. ..
  25. Hain C. [Development of a opioid dependence in a not diagnosed restless legs syndrome]. Psychiatr Prax. 2002;29:322-3 pubmed
  26. Garcia del Pozo J, Carvajal A, Rueda de Castro A, Cano del Pozo M, Martin Arias L. Opioid consumption in Spain--the significance of a regulatory measure. Eur J Clin Pharmacol. 1999;55:681-3 pubmed
    ..For the five drugs that require a special prescription form (morphine, methadone, pethidine, tilidine and fentanyl), the consumption has increased 13.5-fold. A huge increase in opioid consumption has occurred...
  27. van der Hooft J, De Vos R, Mihaleva V, Bino R, Ridder L, de Roo N, et al. Structural elucidation and quantification of phenolic conjugates present in human urine after tea intake. Anal Chem. 2012;84:7263-71 pubmed publisher
  28. Zivanov Stakić D, Solomun L, Zivanovic L. High-performance liquid chromatographic determination of tilidine in pharmaceutical dosage forms. Farmaco. 1989;44:759-62 pubmed
    A reversed-phase high performance liquid chromatographic method for the determination of tilidine in bulk drug and its liquid and solid dosage forms is described. The method uses reversed-phase column RP-8 with methanol -0...
  29. Martin W, Ring J, Gaupp M, Arnold P, Sennewald R, Doser K. Bioavailability investigation of a new tilidine/naloxone liquid formulation compared to a reference formulation. Arzneimittelforschung. 1999;49:599-607 pubmed
    An oral solution available as ethanol-free droplets of the fixed drug combination tilidine-HCl 50 mg/naloxone-HCl 4 mg (CAS 27107-79-5 and CAS 465-65-6, respectively; Tilidin-ratiopharm plus Tropfen) was investigated in 12 healthy ..
  30. Grun B, Krautter S, Riedel K, Mikus G. Inhibition of the active principle of the weak opioid tilidine by the triazole antifungal voriconazole. Br J Clin Pharmacol. 2009;68:712-20 pubmed publisher
    ..of the potent CYP2C19 and CYP3A4 inhibitor voriconazole on the pharmacokinetics and analgesic effects of tilidine. Sixteen healthy volunteers received voriconazole (400 mg) or placebo together with a single oral dose of ..
  31. Thierry C, Boeynaems J, Paolo M. Actions of tilidine and nortilidine on cloned opioid receptors. Eur J Pharmacol. 2005;506:205-8 pubmed
    b>Tilidine, alone or combined with naloxone to prevent drug abuse, is used as an oral opioid analgesic...
  32. Musshoff F, Trafkowski J, Kuepper U, Madea B. An automated and fully validated LC-MS/MS procedure for the simultaneous determination of 11 opioids used in palliative care, with 5 of their metabolites. J Mass Spectrom. 2006;41:633-40 pubmed
    ..buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, piritramide, tilidine, and tramadol together with their metabolites bisnortilidine, morphine-glucuronides, norfentanyl, and nortilidine ..
  33. Carvajal A, Garcia del Pozo J, Martin Arias L, Martin de Diego I, Rueda A, Caro Patón T, et al. [Changes in the pattern of opioid analgesic consumption in Spain]. Med Clin (Barc). 1997;109:281-3 pubmed
    ..Availability of new analgesic opioid drugs with better pharmacokinetic profiles has contributed to an increase of their consume in Spain. ..
  34. Grun B, Merkel U, Riedel K, Weiss J, Mikus G. Contribution of CYP2C19 and CYP3A4 to the formation of the active nortilidine from the prodrug tilidine. Br J Clin Pharmacol. 2012;74:854-63 pubmed publisher
    The analgesic activity of tilidine is mediated by its active metabolite, nortilidine, which easily penetrates the blood-brain barrier and binds to the µ-opioid receptor as a potent agonist...
  35. Weiss J, Sawa E, Riedel K, Haefeli W, Mikus G. In vitro metabolism of the opioid tilidine and interaction of tilidine and nortilidine with CYP3A4, CYP2C19, and CYP2D6. Naunyn Schmiedebergs Arch Pharmacol. 2008;378:275-82 pubmed publisher
    b>Tilidine is one of the most widely used narcotics in Germany and Belgium. The compound's active metabolite nortilidine easily penetrates the blood-brain barrier and activates the mu-opioid receptor...
  36. von Renteln Kruse W, Sarnow E, Schenkel I. [Chronic pain due to degenerative and inflammatory musculoskeletal diseases in the elderly. Observational study investigating dosage, course of treatment, effectiveness and tolerability of tilidine/naloxone]. MMW Fortschr Med. 2005;147:41 pubmed
  37. Gille J, Gille M, Gahr R, Wiedemann B. [Acute pain management in proximal femoral fractures: femoral nerve block (catheter technique) vs. systemic pain therapy using a clinic internal organisation model]. Anaesthesist. 2006;55:414-22 pubmed
    ..Group B (n=50) initially received intravenous metamizol (1 g) and a fixed combination of oral tilidine (100 mg) + naloxone (8 mg)...