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Tramadol is a centrally acting analgesic which possesses opioid agonist properties and activates monoaminergic spinal inhibition of pain. It may be administered orally, rectally, intravenously or intramuscularly. In patients with moderate to severe postoperative pain, intravenous or intramuscular tramadol has generally proved to be of equivalent potency to pethidine (meperidine) and one-fifth as potent as nalbuphine. Intravenous tramadol 50 to 150mg was equivalent in analgesic efficacy to morphine 5 to 15mg in patients with moderate pain following surgery; however, when administered epidurally tramadol was one-thirtieth as potent as morphine. Tramadol has demonstrated efficacy in a few studies in the short term treatment of chronic pain of various origins. Orally administered tramadol was found to be an effective analgesic in step 2 of the World Health Organization’s guidelines for the treatment of patients with cancer pain.
Tramadol is well tolerated in short term use with dizziness, nausea, sedation, dry mouth and sweating being the principal adverse effects. Respiratory depression has been observed in only a few patients after tramadol infusion anaesthesia. When used for pain relief during childbirth, intravenously administered tramadol did not cause respiratory depression in neonates. The tolerance and dependence potential of tramadol during treatment for up to 6 months appears to be low, although the possibility of dependence with long term use cannot be entirely excluded.
Thus, evidence to date of the analgesic effectiveness of tramadol combined with a low respiratory depressant effect and low dependence potential in short term use, suggests that the drug may become a useful alternative to the opioid analgesics currently available for the treatment of patients with moderately severe acute or chronic pain.
Tramadol is a centrally acting analgesic which acts at opioid receptors and also appears to modify transmission of pain impulses by inhibition of monoamine reuptake. Tramadol has demonstrated analgesic activity in a number of animal models. In healthy volunteers with experimentally induced pain, oral tramadol exhibited analgesic activity similar to that of dextropropoxyphene and was more effective than flupirtine or dipyrone (metamizole) but less effective than tilidine. The duration of analgesia with orally administered tramadol was 3 to 6 hours, with maximum pain relief reported at 1 to 4 hours post-dose. Intravenous tramadol 2 mg/kg was as effective as pethidine (meperidine) 1 mg/kg.
In healthy volunteers, intravenous tramadol produced a slight dose-dependent respiratory depression. Tramadol administered intravenously to postoperative patients either produced no change in partial pressure of CO2 or a clinically nonsignificant increase. Tramadol 0.5 to 2 mg/ kg produced a nonsignificant increase in end-tidal CO2 whereas morphine 0.143 mg/kg elicited a significant increase. After intravenous administration tramadol tended to produce transient changes in heart rate and blood pressure in the first 5 to 10 minutes postinjection. The respiratory depressant and haemodynamic effects elicited by tramadol are unlikely to be clinically significant at the recommended parenteral dosage. Epidemiological data suggest that tramadol has a low abuse potential. It appears from tolerance and physical dependence tests in animals and humans that tramadol has a low physical dependence potential. However, during long term treatment the possibility of physical dependence cannot be entirely excluded.
After oral administration as capsules or tablets, tramadol appears in the plasma within 15 to 45 minutes, reaching peak plasma concentrations at a mean of 2 hours. The absolute oral bio-availability of tramadol is approximately 68% after single doses and increases to 90 to 100% on multiple administration. Tramadol has a high tissue affinity with apparent volumes of distribution of 306 and 203L after oral and intravenous administration, respectively, in healthy volunteers.
Tramadol undergoes hepatic metabolism, with approximately 85% of an oral dose being metabolised in young healthy volunteers. Only 1 metabolite, O-demethyl tramadol, is pharmacologically active. The mean elimination half-life of tramadol following oral or intravenous administration is 5 to 6 hours. Approximately 90% of an oral dose is excreted via the kidneys. The elimination half-life is increased approximately 2-fold in patients with impaired hepatic or renal function. On coadministration with the hepatic enzyme inducer carbamazepine, the elimination half-life of tramadol is decreased.
The analgesic efficacy of oral, parenteral or rectal tramadol has been established in large multicentre phase IV trials with 73 to 94% of patients obtaining satisfactory pain relief depending on the cause of pain. In postoperative pain states using patient-controlled analgesia (PCA), intravenously administered tramadol was equivalent to pethidine, one-fifth as potent as nalbuphine and one-thousandth as potent as fentanyl. Tramadol administered epidurally was one-thirtieth as potent as morphine in patients following abdominal surgery, and was superior in analgesic efficacy to bupivacaine. Intravenous tramadol 50 to 150mg was equivalent in analgesic efficacy to morphine 5 to 15mg in the treatment of patients with moderate, but not severe, postoperative pain. In other postoperative pain states the analgesic effect of intramuscular tramadol 50mg was similar to that of pentazocine 30mg, nefopam 20mg, and dipyrone 1500mg but less effective than nicomorphine 10mg and buprenorphine 0.3mg. Following surgery in paediatric patients, tramadol was as effective and one-fifth as potent as nalbuphine, both administered intramuscularly. In most studies the peak analgesic effect of intramuscularly administered tramadol occurred in 1 to 2 hours and analgesia lasted for 5 to 6 hours. Orally administered tramadol 50mg was equivalent to pentazocine 50mg in the relief of pain in patients following osteosynthesis.
In obstetric analgesia intramuscular tramadol 50 to 150mg was generally found to be equivalent to intramuscular pethidine 50 to 100mg and tramadol 100mg was equivalent to morphine 10mg. In the short term treatment of various chronic pain states intramuscular tramadol 50 and 100mg was equivalent to pentazocine 30mg but less effective than pentazocine 60mg and oral tramadol 50mg was more effective than tilidine 50mg. A daily dose of tramadol 250mg to 600mg administered orally was found to be an effective analgesic in step 2 of the World Health Organization’s guidelines for the treatment of patients with cancer pain. Tramadol appeared to be equivalent to sustained release morphine in the treatment of moderate cancer pain but was generally less effective in severe pain.
Tramadol was not found to be a suitable analgesic for use in balanced anaesthesia because of problems with increased intraoperative awareness.
The most common adverse effects associated with tramadol administration are dizziness, nausea, sedation, dry mouth and sweating with an incidence ranging from 2.5 to 6.5%. No clinically relevant respiratory depression has been reported after recommended doses of the drug. In higher than recommended doses after infusion as a supplement to anaesthesia, tramadol caused respiratory depression requiring naloxone in a few patients. In one study tramadol, administered intravenously for pain relief during childbirth, caused respiratory depression in neonates although this was significantly less than that caused by pethidine. The incidence of other opioid-related adverse effects, such as constipation, appears to be low with tramadol.
Tramadol is available for oral, parenteral and rectal use. Tramadol dose should be titrated according to the pain intensity and the response of the individual patient, with 50 to 100mg 4 times daily usually providing adequate pain relief. A total daily dose of 400mg is usually sufficient. Intravenous injections should be administered slowly to reduce the potential for adverse events, particularly nausea. Based on pharmacokinetic data, caution should be observed in patients with renal or hepatic dysfunction as the potential for delayed elimination and accumulation of the drug exists. In these patients the dosage interval should be extended. Tramadol may be used in children at a dosage of 1 to 2 mg/kg.
- Alon E, Atanassof PG, Biro P. Postoperative intravenous analgesia with nalbuphine and tramadol. Continuous infusion combined with patient-controlled application. In German. An-aesthesist 41: 83–87, 1992.
- Alon E, Schulthess G, Axhausen Ch, Hossli G. A double blind comparison of tramadol and buprenorphine in the control of postoperative pain. In German. Anaesthesist 30: 623–626, 1981.
- Anonymous. Tramadol prescribing information, Germany, 1991.
- Arend I, von Arnim B, Nijssen J, Scheele J, Flohé L. Tramadol and pentazocine in a double-blind crossover comparison. In German. Arzneimittel-Forschung/Drug Research 28: 199–208, 1978.
- Barth H, Durra S, Giertz H, Goroll D, Flohe L. Long-term administration of the centrally acting analgesic tramadol did not induce dependence or tolerance. Abstract no. 439. Pain (Suppl. 4): S231, 1987b.
- Barth H, Giertz H, Schmal A, Lorenz W. Anaphylactoid reactions and histamine release do not occur after application of the opioid tramadol. Agents and Actions 20: 310–313, 1987a.
- Becker R, Lintz W. Determination of tramadol in human serum by capillary gas chromatography with nitrogen-selective detection. Journal of Chromatography 377: 213–220, 1986.
- Berghold F, Aufmesser H, Aufmesser W, Schlederer M, Schnell K. Erstversorgung von Wintersportverletzungen. Analgetische Wirksamkeit und Verträglichkeit von Tramadol. Therapiewoche Österreich 6: 173–184, 1991.
- Bernatzky G, Jurna I. Intrathecal injection of codeine, buprenorphine, tilidine, tramadol and nefopam depresses the tail-flick response in rats. European Journal of Pharmacology 120: 75–80, 1986.
- Bianchetti MG, Beutler A, Ferner PE. Intoxication sévère avec un opiacé (Tramadol) chez un nourrisson de cinq semaines. Helvetica Paediatrica Acta 43: 241–244, 1988.
- Bitsch M, Emmrich J, Hary J, Lippach G, Rindt W. Geburtshilfliche Analgesie mit Tramadol. Fortschritte der Medizin 98: 632–634, 1980.
- Bromm B, Herrmann WM, Scharein E. Comparison of two effective analgesics — experimental study: tramadol versus tilidine/naloxone. In German. Fortschritte der Medizin 107: 385–389, 1989.
- Carilo NB, Cordova S. A comparative clinical study of tramadol 100mg versus tramadol 50mg. Current Therapeutic Research 51: 112–120, 1992.
- Carlsson K-H, Jurna I. Effects of tramadol on motor and sensory responses of the spinal nociceptive system in the rat. European Journal of Pharmacology 139: 1–10, 1987.
- Chaturachinda K, Tangtrakul S, Pausawasdi S, Padmasuta K, O-Prasertsawat P. A comparative study of tramadol and pethidine in laparoscopic interval sterilization. Journal of the Medical Association of Thailand 71 (suppl. 1): 55–57, 1988.
- Chrubasik J, Buzina M, Schulte-Mönting J, Atanassoff P, Alon E. Intravenous tramadol for post-operative pain — comparison of intermittent dose regimens with and without maintenance infusion. European Journal of Anaesthesiology 9: 23–28, 1992.
- Chrubasik J, Warth L, Wüst H, Bretschneider H, Schulte-Mönting J, et al. Untersuchung zur analgetischen Wirksamkeit peridural applizierten Tramadols bei der Behandlung von Schmerzen nach abdominalchirurgischen Eingriffen. Schmerz/ Pain/Douleur 9: 12–18, 1988.
- Collait L, Luthy C, Dayer P. Partial inhibition of tramadol antinociceptive effect by naloxone in man. Abstract. British Journal of Clinical Pharmacology 35: 73P, 1993.
- Cossmann M, Wilsmann KM. Anwendung der Tramadol-Injektionslösung (Tramai®) beim akuten Schmerz. Offene Prüfung zur Beurteilung der Akutwirkung und der Verträglichkeit bei einmaliger perenteraler Anwendung. Münchener Medizinische Wochenschrift 130: 633–636, 1988.
- Cossmann M, Wilsmann KM. Behandlung länger andauernder Schmerzsyndrome. Beurteilung der Wirkung und Verträglichkeit von Tramadol (Tramai®) bei mehrmaliger Gabe. Münchener Medizinische Wochenschrift 129: 851–854, 1987a.
- Cossmann M, Wilsmann KM. Wirkung und Begleitwirkungen von Tramadol. Offene Phase-IV-Prüfung mit 7198 Patienten. Therapiewoche 37: 3475–3485, 1987b.
- Delilkan AE, Vijayan R. Forum. Epidural tramadol for postoperative pain relief. Anaesthesia 48: 328–331, 1993.
- Driessen B, Reimann W. Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro. British Journal of Pharmacology 105: 147–151, 1992.
- Dundee JW, McCaughey W. Drugs in Anaesthetic Practice. In Speight (Ed.) Avery’s drug treatment, 3rd ed., pp 303–359, Adis Press, Auckland, 1987.
- Fassolt A. Tramai® (tramadol) for treatment of pain in the initial postoperative period. In German. Schweizer Rundschau Medizin (Praxis) 69: 1495–1500, 1980.
- Fassolt A. The analgesic effectiveness of Tramai® (tramadol) lOOmg for postoperative wound pain. In German. Schweizer Rundschau Medizin (Praxis) 70: 435–440, 1981.
- Fechner R, Racenberg E, Castor G. Klinische Untersuchungen über die Wirkung von Morphin, Pentazocin, Pethidin, Piritramid und Tramadol auf die Atmung. Anästhesiologie und Intensivmedizin 26: 126–132, 1985.
- Feingold E. Classen W, Tille Ch, Netter P. Comparison of analgesics on different pain stimuli. Abstract no. 12. In German. Arzneimittel-Forschung/Drug Research 32: 901, 1982.
- Flohé L, Arend I, Cogal A, Richter W, Simon M. Clinical study on the development of dependency after long-term treatment with tramadol. In German. Arzneimittel-Forschung/Drug Research 28: 213–217, 1978.
- Frankus E. Friderichs E, Kim SM, Osterloh G. On separation of isomers, structural elucidation and pharmacological characterisation of 1-(m-methoxyphenyl)- 2-(dimethylaminomethyl)-cyclohexan-1-ol. In German. Arzneimittel-Forschung/Drug Research 28: 114–121, 1978.
- Fricke JR Jr, Minn F, Cunningham BD, Angelocci DL, Pateros-Nowak CA. Tramadol HCL: dose response in pain from oral surgery. Abstract no. P111–35. Clinical Pharmacology and Therapeutics 49: 182, 1991.
- Friderichs E, Becker R. Correlation of tramadol and M1 serum levels with antinociceptive activity in mice. Abstract no. 36. Naunyn-Schmiedeberg’s Archives of Pharmacology 343 (Suppl.): 9, 1991.
- Friderichs E, Felgenhauer F, Jongschaap P, Osterloh G. Pharmacological studies on analgesia, dependence and tolerance of tramadol, a potent analgetic drug. In German. Arzneimittel-Forschung/Drug Research 28: 122–134, 1978.
- Friderichs E, Reimann W, Selve N. Contribution of both enantiomers to antinociception of the centrally acting analgesic tramadol. Abstract no P82. Naunyn-Schmiedeberg’s Archives of Pharmacology 346 (suppl. 1): R36, 1992.
- Friedel B. The effect of tramadol on the EEG and the electronystagmogram. In German. Arzneimittel-Forschung/Drug Research 28: 187–189, 1978.
- Goroll D. Tropfenform eines stark wirksamen Analgetikums in der Doppelblmdprüfung. Medizinische Klinik 78: 173–175, 1983.
- Grond S, Zech D, Lynch J, Schug S, Lehmann KA. Tramadol — a weak opioid for relief of cancer pain. Pain Clinic 5: 241–247, 1992.
- Hackl W, Fitzal S, Lackner F, Weindlmayr-Goettel M. Fentanyl or tramadol in patient-controlled analgesia for treatment of postoperative pain. In German. Anaesthesist 35: 665–671, 1986.
- Hennies H-H, Friderichs E, Schneider J. Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. Arzneimittel-Forschung/Drug Research 38: 877–880, 1988.
- Houmes R-JM, Voets MA, Verkaaik A, Erdmann W, Lachmann B. Efficacy and safety of tramadol versus morphine for moderate and severe postoperative pain with special regard to respiratory depression. Anesthesia and Analgesia 74: 510–514, 1992.
- Huber HP. Examination of psychic effects of a new analgesic agent of the cyclohexanol series. In German. Arzneimittel-Forschung/Drug Research 28: 189–191, 1978.
- Husslein P, Kubista E, Egarter Ch. Obstetric analgesia with tramadol-results of a prospective randomized comparison with pethidine. In German. Zeitschrift für Geburtshilfe und Perinatologie 191: 234–237, 1987.
- Jaffe JH, Martin WR. Opioid analgesics and antagonists. In Goodman Gilman et al. (Eds) The pharmacological basis of therapeutics, 8th ed., pp. 485–521, Pergamon Press, New York, 1991.
- Jellinek H, Haumer H, Grubhofer G, Klappacher G, Jenny T, et al. Tramadol for treatment of postoperative pain. A comparison of patient-controlled analgesia and continuous infusion. In German. Anaesthesist 39: 513–520, 1990.
- Kainz C, Joura E, Obwegeser R, Plöckinger B, Gruber W. Efficacy and tolerance of tramadol with or without antiemetic compared to pethidine in obstetric analgesia. In German. Zeitschrift für Geburtshilfe und Perinatologie 196: 78–82, 1992.
- Karsch KR, Wiegand V, Blanke H, Kreuzer H. Effect of a new analgesic (tramadol) on haemodynamics in patients with coronary heart disease. In German. Zeitschrift für Kardiologie 68: 599–603, 1979.
- Kayser V, Besson J-M, Guilbaud G. Effects of the analgesic agent tramadol in normal and arthritic rats: comparison with the effects of different opioids, including tolerance and cross-tolerance to morphine. European Journal of Pharmacology 195: 37–45, 1991.
- Kayser V, Besson J-M, Guilbaud G. Evidence for a noradrenergic component in the antinociceptive effect of the analgesic agent tramadol in an animal model of clinical pain, the arthritic rat. European Journal of Pharmacology 224: 83–88, 1992.
- Keup W. Missbrauchsmuster bei abhängigkeit von alkohol, medikamenten und drogen: frühwarnsystem-daten für die bundesrepublik Deutschland 1976–1990. Lambertus, Freiberg im Breisgau, 1993.
- Keup W. Zentral wirksame Analgetika: Missrauch als Drogen-Ersatzmittel. Deutsches Ärzteblatt 81: 2561–2566, 1984.
- Klose R, Ehrhart A, Jung R. The influence of buprenorphine and tramadol on the postoperative CO2) response after general anaesthesia. In German. Anästhesiologie und Intensivemedizin Notfallmedizin 17: 29–34, 19
- Krueger H, Müller-Limmroth W. Algo-pupillometric investigation of the analgesic effect of tramadol. In German. Arzneimittel-Forschung/Drug Research 28: 176–178, 1978.
- Lehmann KA, Brand-Stavroulaki A, Dworzak H. The influence of demand- and loading dose on the efficacy of postoperative patient-controlled analgesia with tramadol. A randomized double-blind study. Schmerz/Pain/Douleur 7: 146–152, 1986.
- Lehmann KA, Horrichs G, Hoeckle W. Tramadol as an intraoperative analgesic. A randomised double-blind study with placebo. In German. Anaesthesist 34: 11–19, 1985a.
- Lehmann KA, Jung C, Hoeckle W. Tramadol und Pethidin zur post-operativen Schmerztherapie: Eine randomisierte Doppelblindstudie unter den Bedingungen der intravenösen On-Demand Analgesic Schmerz/Pain/Douleur 6: 88–100, 1985b.
- Lehmann KA, Kratzenberg U, Schroeder-Bark B, Horrichs-Haermeyer G. Postoperative patient-controlled analgesia with tramadol: analgesic efficacy and minimum effective concentrations. Clinical Journal of Pain 6: 212–220, 1990.
- Lehmann KA, Krauskopf K-H. Awareness during balanced anaesthesia. A randomized double-blind study with fentanyl, pentazocine and ketamine. In German. Anaesthesist 41: 373–385, 1992.
- Lenzhofer R, Moser K. Analgesic effect of tramadol in patients with malignant disease. In German. Wiener Medizinische Wochenschrift 134: S199–202, 1984.
- Liao S, Hill JF, Nayak RK. Pharmacokinetics of tramadol following single and multiple oral doses in man. Abstract no. PPDM 8206. Pharmaceutical Research 9 (Suppl.): 308, 1992.
- Lintz W, Barth H, Osterloh G, Schmidt-Böthelt E. Bioavailability of enterai tramadol formulations. Arzneimittel-Forschung/Drug Research 36: 1278–1283, 1986.
- Lintz W, Erlacin S, Frankus E, Uragg H. Biotransformation of tramadol in man and animal. In German. Arzneimittel-Forschung/Drug Research 31: 1932–1943, 1981.
- Lintz W, Uragg H. Quantitative determination of tramadol in human serum by gas chromatography-mass spectrometry. Journal of Chromatography 341: 65–79, 1985.
- Mattia A, Vanderah T, Raffa RB, Vaught JL, Tallarida RJ, et al. Characterization of the unusual antinociceptive profile of tramadol in mice. Drug Development Research 28: 176–182, 1993.
- Mehlisch DR, Minn F, Brown P. Tramadol hydrochloride: efficacy compared to codeine sulfate, acetaminophen with dextropropoxyphene and placebo in dental-extraction pain. Abstract no. P111–34. Clinical Pharmacology and Therapeutics 47: 187, 1990.
- Mikic Z, Banic B, Stanulovic M, Somer T. Clinical evaluation of the analgetic tramadol in the form for oral use. In Serbocroatian. Acta Orthopaedica Iugoslavica 16: 93–96, 1985.
- Monasky MS, Zinsmeister AR, Stevens CW, Yaksh TL. Interaction of intrathecal morphine and ST-91 on antinociception in the rat: dose-response analysis, antagonism and clearance. Journal of Pharmacology and Experimental Therapeutics 254: 383–392, 1990.
- Moroz BT, Ignatov YU, Kalinin VI. Use of tramadol hydrochloride in therapeutic operative dentistry: clinical investigation. Current Therapeutic Research 49: 371–375, 1991.
- Müller H, Stoyanov M, Branler G, Hempelmann G. Effects of tramadol on haemodynamics and respiration during N20−02-ventilation and in the postoperative period. In German. Anaesthesist 31: 604–610, 1982.
- Müller-Limmroth W, Krueger H. The effect of tramadol on psychic and psychomotor performance in man. In German. Arzneimittel-Forschung/Drug Research 28: 179–180, 1978.
- Murano T, Yamamoto H, Endo N, Kudo Y, Okada N, et al. Studies of dependence on tramadol in rats. Arzneimittel-Forschung/Drug Research 28: 152–158, 1978.
- Neal MJ. Medical Pharmacology at a Glance. Blackwell Scientific Publications, Oxford, 1987.
- Nickel B, Aledter A. Comparative physical dependence studies in rats with flupirtine and opiate receptor stimulating analgesics. Postgraduate Medical Journal 63 (suppl. 3): 41–43, 1987.
- Osipova NA, Novikov GA, Beresnev VA, Loseva NA. Analgesic effect of tramadol in cancer patients with chronic pain: a comparison with prolonged-action morphine sulfate. Current Therapeutic Research 50: 812–821, 1991.
- Paar WD, Frankus P, Dengler HJ. The metabolism of tramadol by human liver microsomes. Clinical Investigation 70: 708–710, 1992.
- Padmasuta K. The use of tramadol in analgesic-supplemented anesthesia. Current Therapeutic Research 41: 899–902, 1987.
- Padmasuta K, Pausawasdi S, Tangtrakul S, Chaturachinda K. The efficacy of tramadol in interval laparoscopic sterilization: a comparison of two dosage regimen. Journal of the Medical Association of Thailand 71 (suppl. 2): 61–63, 1988.
- Palme G, Munck A. Prämedikation mit Tramai bei der Laparoskopie. Die Medizinische Welt 32: 28–30, 1981.
- Paravicini D, Trauner K, Lawin P. Tramadol-infusion anaesthesia with substitution of enflurane and various nitrous oxide concentrations. In German. Anaesthesist 34: 20–27, 1985.
- Paravicini D, Zander J, Hansen J. Effects of tramadol on haemodynamics and blood gases in the early postoperative period. In German. Anaesthesist 31: 611–614, 1982.
- Parth P, Madler Ch, Morawetz RF. Analgesic effects of pethidine and tramadol as assessed by experimentally induced pain in man: a double blind comparison. In German. Anaesthesist 33: 235–239, 1984.
- Pausawasdi S, Jirasirithum S, Phanarai C. The use of tramadol hydrochloride in the treatment of post-anesthetic shivering. Journal of the Medical Association of Thailand 73: 16–20, 1990.
- Prasertsawat PO, Herbabutya Y, Chaturachinda K. Obstetric analgesia: comparison between tramadol, morphine, and pethidine. Current Therapeutic Research 40: 1022–1028, 1986.
- Preston KL, Jasinski DR, Testa M. Abuse potential and pharmacological comparison of tramadol and morphine. Drug and Alcohol Dependence 27: 7–17, 1991.
- Primus G, Pummer K, Vucsina F, Meindl N. Tramadol versus metamizole in ureteral colic. In German. Urologe Ausgabe A 28: 103–105, 1989.
- Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, et al. Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol. Journal of Pharmacology and Experimental Therapeutics, in press, 1993.
- Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, et al. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. Journal of Pharmacology and Experimental Therapeutics 260: 275–285, 1992.
- Rettig G, Kropp L. Analgesic effect of tramadol in acute myocardiol infarction. In German. Therapiewoche 30: 5561–5566, 1980.
- Richter W, Barth H, Flohé L, Giertz H. Clinical investigation on the development of dependence during oral therapy with tramadol. Arzneimittel-Forschung/Drug Research 35: 1742–1744, 1985.
- Richter W, von Arnim B, Giertz H. Double-blind clinical trial of tramadol capsules. In German. Münchener Medizinische Wochenschrift 123: 517–520, 1981.
- Riedel F, von Stockhausen H-B. Severe cerebral depression after intoxication with tramadol in a 6-month-old infant. European Journal of Clinical Pharmacology 26: 631–632, 1984.
- Rodrigues N, Rodrigues Pereira E. Tramadol in cancer pain. Current Therapeutic Research 46: 1142–1148, 1989.
- Rohdewald P, Granitzki HW, Neddermann E. Comparison of the analgesic efficacy of metamizole and tramadol in experimental pain. Pharmacology 37: 209–217, 1988.
- Rost A, Schenck EG. The effect of tramadol and other analgesics on the pain threshold in human dental pulp. In German. Arzneimittel-Forschung/Drug Research 28: 181–183, 1978.
- Rothe KF, Brather R. Postoperative depression of respiration because of infusion anaesthesia with tramadol? In German. Anaesthesist 32: 88, 1983.
- Rothhammer A, Weis KH, Skrobek W. The clinical usefulness of tramadol-infusion anaesthesia. In German. Anaesthesist 30: 619–622, 1981.
- Sawynok J. The 1988 Merck Frosst Award. The role of ascending and descending noradrenergic and serotonergic pathways in opioid and non-opioid antinociception as revealed by lesion studies. Canadian Journal of Physiology and Pharmacology 67: 975–988, 1989.
- Schärfer J, Hagemann H, Holzapfel S, Panning B, Piepenbrock S. Investigation of tramadol for postoperative analgesia in children. In German. Fortschritte der Anästhesiologie 3: 42–45, 1989.
- Schäffer J, Piepenbrock S, Kretz F-J, Schönfeld C. Nalbuphine and tramadol for the control of operative pain in children. In German. Anaesthesist 35: 408–413, 1986.
- Schenck EG, Arend I. Clinical trial of tramadol by means of the ‘paired card’ system. In German. Arzneimittel-Forschung/Drug Research 28: 196–199, 1978.
- Seitz W, Lübbe N, Fritz K, Sybrecht G, Kirchner E. Effects of tramadol on respiratory CO2 response and mouth occlusion pressure. In German. Anaesthesist 34: 241–246, 1985.
- Sevcik J, Harms L, Illes P. Effect of tramadol and its main metabolite O-desmethyltramadol on locus coeruleus neurones. Abstract no P26. Naunyn-Schmiedebergs Archives of Pharmacology 346 (suppl.1): R22, 1992.
- Sommer F. Klinische Prüfung mit dem Analgetikum Tramadol-HCL. Erfahrungsbericht aus einer orthopädischen Praxis. Extracta Medica Practia 2: 826–831, 1981.
- Staritz M, Poralla T, Manns M, Meyer Zum Büschenfelde K-H. Effect of modern analgesic drugs (Tramadol, pentazocine and buprenorphine) on the bile duct sphincter in man. Gut 27: 567–569, 1986.
- Stoffregen J. Infusion-controlled tramadol anaesthesia. In German. Anaesthesist 29: 673–674, 1980.
- Striebel HW, Hackenberger J. Comparison of tramadol/metamizole infusion versus combined tramadol infusion and ibuprofen suppositories for postoperative pain management after hysterectomy. In German. Anaesthesist 41: 354–360, 1992.
- Sunshine A, Olson NZ, Zighelboim I, DeCastro A, Minn FL. Analgesic oral efficacy of tramadol hydrochloride in postoperative pain. Clinical Pharmacology and Therapeutics 57: 740–746, 1992.
- Suvonnakote T, Thitadilok W, Atisook R. Pain relief during labour. Journal of the Medical Association of Thailand 69: 576–580, 1986.
- Szekely SM, Vickers MD. A comparison of the effects of codeine and tramadol on laryngeal reactivity. European Journal of An-aesthesiology 9: 111–120, 1992.
- Tawfik MO, Elborolossy K, Nasr F. Tramadol hydrochloride in the relief of cancer pain. A double blind comparison against sustained release morphine. Abstract no. 188. Pain (Suppl. 5): S377, 1990.
- Vickers MD, O’Flaherty D, Szekely SM, Read M, Yoshizumi J. Tramadol: pain relief by an opioid without depression of respiration. Anaesthesia 47: 291–296, 1992.
- Vogel W, Burchardi H, Sihler K, Valič L. The effect of tramadol, a new analgesic, on respiration and cardiovascular function. In German. Arzneimittel-Forschung/Drug Research 28: 183–186, 1978.
- Voorhees F, Leibold DG, Stumpf A, Fite F, Crook F, et al. Tramadol: efficacy compared with codeine, aspirin with codeine, and placebo in dental extraction pain. Abstract no. PI-3. Clinical Pharmacology and Therapeutics 51: 122, 1992.
- Yanagita T. Drug dependence potential of 1-(m-methoxyphenyl) -2-(dimethylaminomethyl) -cyclohexan-1-ol hydrochloride (Tramadol) tested in monkeys. Arzneimittel-Forschung/Drug Research 28: 158–163, 1978.
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