Bratisl Lek Listy. 1995 Dec;96(12):669-70.
[Postoperative analgesia with epidural administration of a combination of tramadol and clonidine]

[Article in Slovak]

Masar O, Zelinkova M, Pechan J, Krcmery S, Hanuskova D, Buzukasvili M.

Anesteziologicko-resuscitacne oddelenie, II. chirurgicka klinika LFUK, Bratislave.

Postoperative analgesia inhibits the stress cascade with negative effects on whole organism. Therefore the spectrum of drugs used for soothing postoperative pain quickly widens. The epidural route appears as being logical, since due to the direct effect in the transmission and processing of pain it suffices with a lower dosage. The authors refer to a group of 30 patients postoperatively treated by a combination of tramadol and Clonidine administrated by means of an epidural catheter. 26 patients evaluated the induced analgesia as excellent or sufficient. (Tab. 3, Ref. 4).

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8624752&dopt=Abstract tramadol Ultram




Lijec Vjesn. 1995 Jun;117 Suppl 2:112-3.
Analgesia at the department of intensive care.

Kolonic V.

Institute of Oncology, Ljubljana, Slovenia.

Analgesia at the Department of intensive care can be distributed into three groups, with respect to the patient's respiratory status: 1) analgesia in a patient on controlled ventilation; 2) analgesia in a patient who is being weaned from a respirator; 3) analgesia in a patient breathing spontaneously. In patients of group 1, analgesia, respiratory depression and sedation are achieved with morphine applied parenterally or epidurally. While patients on assisted ventilation (group 2) require good analgesia and sedation, they should remain cooperative; this is achieved with tramadol or ketamine. Spontaneously breathing patients are maintained on tramadol in combination with NSAID. In all patients the dosage needs to be adjusted with respect to the type of pain, age, nutrition status, and previous use of analgesics.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8649139&dopt=Abstract tramadol Ultram




Eur J Pharmacol. 1996 Dec 5;316(2-3):369-72.
Tramadol, M1 metabolite and enantiomer affinities for cloned human opioid receptors expressed in transfected HN9.10 neuroblastoma cells.

Lai J, Ma SW, Porreca F, Raffa RB.

Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, USA.

Tramadol hydrochloride is a centrally acting synthetic analgesic in widespread clinical use. Despite different degrees of opioid-like characteristics in preclinical tests, it is characterized by lack of full naloxone reversibility or naloxone-precipitated withdrawal in humans. To investigate this apparent discrepancy, the present study measured the affinity of tramadol (and its enantiomers) and an active O-desmethyl metabolite (M1) (and its enantiomers) to cloned human opioid receptors of the mu, delta and kappa type stably expressed in HN9.10 neuroblastoma cells. At mu sites, the Ki values for tramadol, its (+) and (-) enantiomers, M1, and its (+) and (-) enantiomers were 17000, 15700, 28800, 3190, 153 and 9680 nM, respectively, compared to 7.1 nM for morphine. These results are consistent with the suggestion of a non-opioid contribution to the clinical profile of tramadol.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8982709&dopt=Abstract tramadol Ultram




Sud Med Ekspert. 1996 Oct-Dec;39(4):38-43.
[The detection of tramadol and its metabolites in urine by chromatographic methods]

[Article in Russian]

Veselovskaia NV, Kislun IuV, Eremin SK, Izotov BN, Viatchanina AP, Dorogokupets OB, Morozova EB, Kovalenko AE.

The authors recommend detecting a compound drug tramadol and its metabolites in urinary extracts by thin-layer, gas-chromatographic, high-pressure liquid, and other chromatographic methods. The metabolites were identified with due consideration for their fragmentation during an electron strike thereof and their trimethylsilyl derivatives, mobility during separation in a thin layer, and results of selective extraction at various pH. The proposed scheme of biotransformation includes the formation of products of O- and N- demethylation, N, N- and N,O-didemethylation and hydroxylation of the cyclohexane fragment. The Rf metabolite values and their mass spectra are presented. During gas chromatographic analysis at an evaporator temperature at least 250 degrees C tramadol undergoes thermal destruction with the formation of water molecules and cyclohexane structure.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9026968&dopt=Abstract tramadol Ultram




J Chromatogr B Biomed Sci Appl. 1997 May 23;693(1):222-7.
Determination of tramadol in human plasma by capillary gas chromatography-mass spectrometry using solid-phase extraction.

Merslavic M, Zupancic-Kralj L.

KRKA Pharmaceuticals, Pharmacokinetics Department, Novo mesto, Slovenia.

An analytical method using solid-phase extraction, capillary gas chromatography and mass selective detection in the electron-impact ionization (EI) mode was developed for the determination of tramadol (2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol) in human plasma. The advantages of this method are the high sensitivity and selectivity and the linearity over the concentration range 2-500 ng/ml. Quantification was made using nefopam as an internal standard, and the detection limit was found to be 1 ng/ml. The standard deviations of the intra-day precision test ranged from 4.5 to 6.0% with respect to the concentration. Accuracy ranged from 1.0 to 4.0% (inter-day). The method was used for the determination of tramadol in a bioequivalence study.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9200539&dopt=Abstract tramadol Ultram