J Chromatogr B Biomed Sci Appl. 2001 Nov 5;763(1-2):165-71.
Gas chromatographic method using nitrogen-phosphorus detection for the measurement of tramadol and its O-desmethyl metabolite in plasma and brain tissue of mice and rats.

Tao Q, Stone DJ Jr, Borenstein MR, Jean-Bart V, Codd EE, Coogan TP, Desai-Krieger D, Liao S, Raffa RB.

Temple University School of Pharmacy, Philadelphia, PA 19140, USA.

A method that allows the measurement of plasma and brain levels of the centrally-acting analgesic tramadol and its major metabolite (O-desmethyl tramadol) in mice and rats was developed using gas chromatography equipped with nitrogen-phosphorus detection (GC-NPD). Plasma samples were extracted with methyl tert.-butyl ether (MTBE) and were injected directly into the GC system. Brain tissue homogenates were precipitated with methanol, the resulting supernatant was dried then acidified with hydrochloric acid. The aqueous solution was washed with MTBE twice, alkalinized, and extracted with MTBE. The MTBE layer was dried, reconstituted and injected into the GC system. The GC assay used a DB-1 capillary column with an oven temperature ramp (135 to 179 degrees C at 4 degrees C/min). Dextromethorphan was used as the internal standard. The calibration curves for tramadol and O-desmethyl tramadol in plasma and brain tissue were linear in the range of 10 to 10000 ng/ml (plasma) and ng/g (brain). Assay accuracy and precision of back calculated standards were within +/- 15%.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11710575&dopt=Abstract tramadol Ultram

biocodex.fr

The activity of nefopam, a centrally acting compound, not structurally related to other analgesics, was examined in acute and postoperative thermal pain models in the rat. Its antinociceptive potency was evaluated using heat noxious stimuli either in intact or in injured animals after skin and muscular incisions. In the hot plate and in the plantar tests, nefopam after acute administration by different routes exhibited a dose-dependent attenuation of the nociceptive responses at 10-30 mg x kg(-1) by intraperitoneal or subcutaneous administration, at 60 mg x kg(-1) by oral dosing, and from 3 mg x kg(-1) after intravenous injection. In the postoperative pain model, at 30 mg x kg(-1) nefopam augmented the endpoint to thermal threshold, 60 and 90 minutes after administration compared to the threshold recorded after the incision. In the same conditions, morphine and tramadol displayed antinociceptive activities. As the plantar test provides a good index of nociception in humans, these results point out the usefulness of nefopam for attenuating moderate to severe pain, and for postoperative analgesia. In conclusion, nefopam has shown potent properties to reduce thermal hypersensitivity after acute or postoperative pain in rats. Copyright 2001 Academic Press.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11735363&dopt=Abstract tramadol Ultram

heinfo.net

AIM: To investigate the distribution of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1), in the central nervous system (CNS). METHODS: After a single ip dose of trans-T hydrochloride or M1, the rats were killed by decapitation. A high performance capillary electrophoresis (HPCE) method was used to determine the concentrations of enantiomers of trans-T and M1 in the serum and different brain tissues, including cerebrospinal fluid (CF), cerebral cortex (CC), corpus striatum (CS), hypothalamus (HY), cerebellum (CE), and medulla oblongata (MO). RESULTS: After ip trans-T hydrochloride, the concentrations of (+)-trans-T were higher than those of (-)-trans-T in the serum and all tested brain tissues; The concentrations of (+)-M1 were lower than those of (-)-M1 in the all tested brain tissues; The concentrations of the enantiomers of trans-T and M1 were the highest in the CC, the lowest in the CF. After ip M1, the concentrations of (+)-M1 were higher than those of (-)-M1 in the serum and all tested brain tissues; The concentrations of the enantiomers of M1 were the highest in the CC, the lowest in the CF. CONCLUSION: The concentrations of the enantiomers of trans-T and M1 varied in the serum and different brain tissues. The distribution of trans-T and M1 in the CNS of rats was stereoselective. The stereoselectivity in the distribution of M1 after M1 injection was different with that after trans-T injection.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11749767&dopt=Abstract tramadol Ultram

onu.edu

The abuse potential of tramadol was investigated using both in vivo microdialysis measures of dopamine (DA) release within the nucleus accumbens (NAc) shell and the conditioned place preference (CPP) paradigm in rats. Tramadol (75 mg/kg, i.p.) induced a statistically significant increase (starting 80 min posttreatment) in DA release within the NAc shell, which was maintained for at least 120 min posttreatment. Tramadol (18.75, 37.5, and 75 mg/kg i.p.) produced a statistically significant CPP, with the effects of the two highest doses comparable to those induced by morphine (5 mg/kg, s.c.). The release of DA within the NAc shell may be responsible for the rewarding properties of tramadol and, together with the CPP results, provide evidence that tramadol may possess greater abuse potential than originally believed. Copyright 2001 Wiley-Liss, Inc.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11754490&dopt=Abstract tramadol Ultram

eucmax.sim.ucm.es

The objectives of this study were first to investigate the compatibility and physical stability of drug admixtures destined for s.c. administration through elastomeric infusion pumps to terminally ill cancer patients followed up at home by staff of the Palliative Care Unit (AECC), "La Paz" Hospital, Madrid and secondly, to evaluate the local side-effects related to the infusion of some of the drug mixtures to a population of 50 patients. The drug mixtures prepared included combinations of two, three, four and five of the following drugs: morphine hydrochloride, 60 mg/day; midazolam hydrochloride, 15 mg/day; haloperidol lactate, 7.5 mg/day; hyoscine-N-butyl-bromide, 60 mg/day; dexamethasone sodium phosphate, 16 mg/day; metoclopramide hydrochloride, 40 mg/day, and tramadol, 400 mg/day. Out of 86 mixtures evaluated in vitro, 52 were found to be physically compatible. Precipitation was always obtained when dexamethasone sodium phosphate at the concentrations assayed was combined with haloperidol lactate and/or midazolam hydrochloride. However, no precipitation occurred when morphine hydrochloride, the opioid most frequently used in patients of this type, and dexamethasone sodium phosphate were combined. Of the drug mixtures that were physically compatible, 18 were administered to the patient population evaluated. Very good symptom control was obtained with all of them, and especially with the mixture of morphine + midazolam + haloperidol + hyoscine, which is the one most frequently administered to cancer patients for palliative care in the final stages of life in our Unit.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11777190&dopt=Abstract tramadol Ultram