Comments on tramadolrx's Journal

ORDER TRAMADOL - USA Pharmacy

Complementary and synergistic antinociceptive interaction between the enantiomers of Tramadol ( Generic Ultram ).

The explanation for the co-existence of opioid and nonopioid components of Tramadol ( Generic Ultram )-induced antinociception appears to be related to the different, but complementary and interactive, pharmacologies of its enantiomers. The (+) enantiomer had Ki values of only 1.33, 62.4 and 54.0 microM at mu, delta and kappa receptors, respectively. The (-) enantiomer had even lower affinity at the mu and delta sites (Ki = 24.8, 213 and 53.5 microM, respectively. The (+) enantiomer was the most potent inhibitor of serotonin uptake (Ki = 0.53 microM) and the (-) enantiomer was the most potent inhibitor of norepinephrine uptake (Ki = 0.43 microM). Basal serotonin release was preferentially enhanced by the (+) enantiomer and stimulation-evoked norepinephrine release was preferentially enhanced by the (-) enantiomer. The (+) and (-) enantiomers each independently produced centrally mediated antinociception in the acetylcholine-induced abdominal constriction test (ED50 = 14.1 and 35.0 micrograms i.t., respectively). Racemic Tramadol ( Generic Ultram ) was significantly more potent (P < .05) than the theoretical additive effect of the enantiomers (antinociceptive synergy). Synergy was also demonstrated (P < .1) in the mouse 55 degrees C hot-plate test (i.p. route) and (P < .05) the rat Randall-Selitto yeast-induced inflammatory nociception model (i.v. and i.p. routes). Critically, the enantiomers interacted less than synergistically in two side-effects of inhibition of colonic propulsive motility and impairment of rotarod performance. The racemate and the (+) enantiomer were active in a chronic (arthritic) inflammatory pain model. Taken together, these findings provide a rational explanation for the coexistence of dual components to Tramadol ( Generic Ultram )-induced antinociception and might form the basis for understanding its clinical profile.

Algo-pupillometric investigation of the analgesic effect of Tramadol ( Generic Ultram ) (author's transl)

1. The analgesic efficacy of 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (Tramadol ( Generic Ultram ); Tramal) (75 and 100 mg) was investigated in 22 young, healthy volunteers by means of an algo-pupillometric method. 2. Tramadal itself causes a slight miosis which becomes statistically significant only 3 h after administration. 3. In the algo-pupillogram the effect of Tramadol ( Generic Ultram ) is shown to be biphasic during the first 80 min. Thereafter the pupillary reaction steadily decreases, reaching a minimum after about 3.5--4 h in both dosages. 4. At the time of maximum effect the pupillary reaction of subjects given 75 or 150 mg Tramadol ( Generic Ultram ) is calculated to be equal to that of untreated individuals to whom only 60% or 10%, respectively, of the stimulus intensity has been applied.

The postoperative analgesic effect of Tramadol ( Generic Ultram ) when used as subcutaneous local anesthetic.Altunkaya H, Ozer Y, Kargi E, Ozkocak I, Hosnuter M, Demirel CB, Babuccu O.Department of Anesthesiology, Zonguldak Karaelmas University, School of Medicine, Ev-Ko Konutlari F-66 No: 8, 67600 Kozlu/Zonguldak, Turkey. Recently, it has been shown that Tramadol ( Generic Ultram ) was an effective local anesthetic in minor surgery. In this study, its efficacy for relieving postoperative pain was evaluated. Forty patients undergoing minor surgery (lipoma excision and scar revision) under local anesthesia were included. The patients were randomly allocated into two groups: In group T (n = 20), 2 mg/kg Tramadol ( Generic Ultram ), and in group L (n = 20), 1 mg/kg lidocaine were given subcutaneously. In both groups, the injection volume was 5 mL containing 1/200,000 adrenalin. The degree of the erythema, burning sensation, and pain at the injection site were recorded. Incision response, which is a degree of the pain sensation during incision, was recorded and graded with the visual analog scale (VAS) 0-10. After incision, VAS values were recorded at 15-min intervals. When the VAS score of the pain during surgery exceeded 4, an additional 0.5 mg/kg of the study drug was injected and this dosage was added to the total amount. Patients were discharged on the same day. Subjects with VAS > or =4 were advised to take paracetamol as needed. No side effects were recorded in either group except for 1 patient complaining of nausea in group T at the 30th min of operation. After 24 h, patients were called and the time of first analgesic use and total analgesic dose taken during the postoperative period were recorded. During the 24 postoperative hours, 18 of 20 (90%) subjects did not need any type of analgesia in group T, whereas this number was 10 (50%) in group L (P < 0.05). The time span before taking first analgesic medication was longer (4.9 +/- 0.3 h) in group T than that of group L (4.4 +/- 0.7 h) (P < 0.05). We propose that Tramadol ( Generic Ultram ) can be used as an alternative drug to lidocaine for minor surgeries because of its ability to decrease the demand for postoperative analgesia.

Analysis of Tramadol ( Generic Ultram ) and its metabolites in human urine

A GC-MS method for the analysis of Tramadol ( Generic Ultram ) and its four metabolites in human urine is described. The urine samples were acid hydrolyzed with hydrochloric acid, cleaned with diethyl ether and extracted with dichloromethane-isopropanol (9:1). After derivatization, the solution was analyzed with GC-MSD. Tramadol ( Generic Ultram ) and its 4 metabolites were detected in urine samples 2-40 hours after oral administration. The recovery of Tramadol ( Generic Ultram ) was 85.2% +/- 5.4 (n = 3), the detection limit was down to 12.5 pg. The derivatization methods was discussed.

Tramadol ( Generic Ultram ), a centrally acting analgesic structurally related to codeine and morphine, consists of two enantiomers, both of which contribute to analgesic activity via different mechanisms. (+)-Tramadol ( Generic Ultram ) and the metabolite (+)-O-desmethyl-Tramadol ( Generic Ultram ) (M1) are agonists of the mu opioid receptor. (+)-Tramadol ( Generic Ultram ) inhibits serotonin reuptake and (-)-Tramadol ( Generic Ultram ) inhibits norepinephrine reuptake, enhancing inhibitory effects on pain transmission in the spinal cord. The complementary and synergistic actions of the two enantiomers improve the analgesic efficacy and tolerability profile of the racemate. Tramadol ( Generic Ultram ) is available as drops, capsules and sustained-release formulations for oral use, suppositories for rectal use and solution for intramuscular, intravenous and subcutaneous injection. After oral administration, Tramadol ( Generic Ultram ) is rapidly and almost completely absorbed. Sustained-release tablets release the active ingredient over a period of 12 hours, reach peak concentrations after 4.9 hours and have a bioavailability of 87-95% compared with capsules. Tramadol ( Generic Ultram ) is rapidly distributed in the body; plasma protein binding is about 20%. Tramadol ( Generic Ultram ) is mainly metabolised by O- and N-demethylation and by conjugation reactions forming glucuronides and sulfates. Tramadol ( Generic Ultram ) and its metabolites are mainly excreted via the kidneys. The mean elimination half-life is about 6 hours. The O-demethylation of Tramadol ( Generic Ultram ) to M1, the main analgesic effective metabolite, is catalysed by cytochrome P450 (CYP) 2D6, whereas N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4. The wide variability in the pharmacokinetic properties of Tramadol ( Generic Ultram ) can partly be ascribed to CYP polymorphism. O- and N-demethylation of Tramadol ( Generic Ultram ) as well as renal elimination are stereoselective. Pharmacokinetic-pharmacodynamic characterisation of Tramadol ( Generic Ultram ) is difficult because of differences between Tramadol ( Generic Ultram ) concentrations in plasma and at the site of action, and because of pharmacodynamic interactions between the two enantiomers of Tramadol ( Generic Ultram ) and its active metabolites. The analgesic potency of Tramadol ( Generic Ultram ) is about 10% of that of morphine following parenteral administration. Tramadol ( Generic Ultram ) provides postoperative pain relief comparable with that of pethidine, and the analgesic efficacy of Tramadol ( Generic Ultram ) can further be improved by combination with a non-opioid analgesic. Tramadol ( Generic Ultram ) may prove particularly useful in patients with a risk of poor cardiopulmonary function, after surgery of the thorax or upper abdomen and when non-opioid analgesics are contraindicated. Tramadol ( Generic Ultram ) is an effective and well tolerated agent to reduce pain resulting from trauma, renal or biliary colic and labour, and also for the management of chronic pain of malignant or nonmalignant origin, particularly neuropathic pain. Tramadol ( Generic Ultram ) appears to produce less constipation and dependence than equianalgesic doses of strong opioids.

Pharmacological mechanisms of action of flupirtine: a novel, centrally acting, nonopioid analgesic evaluated by its discriminative effects in the rat.

Rats were trained to discriminate the novel analgesic flupirtine (10.0 mg/kg i.p., 10 min) from no drug under a two-choice fixed-ratio 5 shock-termination schedule. Flupirtine yielded a dose-response curve with an ED50 of 3.87 mg/kg. The opioid analgesics pentazocine, codeine and Tramadol ( Generic Ultram ) failed to produce flupirtine appropriate responding. The opioid antagonist naltrexone did not antagonize the discriminative effects of flupirtine.