Antidepressant-like effects of Tramadol ( Generic Ultram ) and other central analgesics with activity on monoamines reuptake, in helpless rats.

Affective states are regulated mainly by serotonin and noradrenaline. However the opioid system has been also related to antidepressant-induced mood improvement, and the mu-opioid receptor has been involved in affective responses to a sustained painful stimulus. Similarly, antidepressant drugs induce an antinociceptive effect via both the monoaminergic and opioid systems, probably involving sensorial and affective dimensions of pain. The aim of this study was to test three opiate analgesics, which also inhibit monoamine reuptake, in the learned helplessness model of depression in rats. Helpless rats receiving (+/-)Tramadol ( Generic Ultram ) (10, 20 mg/Kg) or (-)methadone (2, 4 mg/Kg) showed a decreased number of failures to avoid or escape aversive stimulus (shock) in both the second and the third daily sessions, compared with controls. Rats receiving levorphanol (0.5, 1 mg/Kg) showed a decreased number of such failures in the third session. The number of crossings in the intertrial interval (ITI) was not significantly modified by (+/-)Tramadol ( Generic Ultram ) or (-)methadone. Levorphanol enhanced ITI crosses at 1 mg/Kg. These results, together with other clinical and experimental data, suggest that analgesics with monoaminergic properties improve mood and that this effect may account for their analgesic effect in regulating the affective dimension of pain. From this, it seems probable that the analgesic effect of opiates could be induced by adding together the attenuation produced of both the sensorial and the affective dimensions of pain.


Treatment of pain with sustained-release Tramadol ( Generic Ultram ) 100, 150, 200 mg: results of a post-marketing surveillance study.

A new simple behavioral method was used for the evaluation of the anti-hyperalgesic properties of Tramadol ( Generic Ultram ) in the rat. At the lowest dose (1.25 mg/kg i.p.), Tramadol ( Generic Ultram ) did not modify thermal nociceptive thresholds, but it was able to prevent and block thermal hindpaw hyperalgesia induced by the tail injection of formalin. Our results provide evidence that Tramadol ( Generic Ultram ) blocks hyperalgesic behaviors without altering nociception, suggesting that this analgesic drug might represent a valid agent against central sensitization. Copyright 1998 Elsevier Science B.V. All rights reserved.


Pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, enhances the analgesic effect of Tramadol ( Generic Ultram ).

The ability of pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, to enhance the clinical antidepressant response to selective serotonin re-uptake inhibitors is generally attributed to a blocking of the feedback that inhibits the serotoninergic neuronal activity mediated by somatodendritic 5-hydroxytryptamine (5-HT)(1A) autoreceptors. The current study examined the ability of pindolol to enhance the analgesic effect of Tramadol ( Generic Ultram ), an atypical centrally-acting analgesic agent with relatively weak opioid receptor affinity and which, like some antidepressants, is able to inhibit the re-uptake of 5-HT in the raphe nuclei. Racemic pindolol (2 mg/kg, s.c.), rendered analgesic a non-effective acute dose of Tramadol ( Generic Ultram ) (10-40 mg/kg, i.p.) in two nociceptive tests: a hot plate test in mice and a plantar test in rats. Moreover, (+/-)8-OH-DPAT (0.125-1 mg/kg, s.c.), a selective 5-HT(1A) agonist, reduces the analgesic effect of Tramadol ( Generic Ultram ) in the same tests. These results suggest an implication of the somatodendritic 5-HT(1A) receptors in the analgesic effect of Tramadol ( Generic Ultram ) and open a new adjuvant analgesic strategy for the use of this compound.


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. The mixed alpha-1/alpha-2 adrenergic agonist clonidine and the highly specific alpha-2 adrenergic agonist UK-14304, both partially and dose-dependently produced flupirtine appropriate responding. The mixed alpha-1/alpha-2 antagonist yohimbine and the highly specific alpha-2 antagonists idazoxan and L-654,284 all partially and dose-dependently antagonized flupirtine appropriate responding. Neither of the alpha-1 agonists phenylephrine or ST 587 produced flupirtine appropriate responding, nor did the alpha-1 antagonist prazosin antagonize flupirtine responding. It is concluded that the discriminative effects of flupirtine are neither of opioid nor of alpha-1 adrenergic type, but are primarily mediated through alpha-2 adrenergic mechanisms.

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.

Withdrawal syndrome and dependence: Tramadol ( Generic Ultram ) too.

(1) Tramadol ( Generic Ultram ) carries a risk of dependence and abuse, even in patients with no history of drug abuse. (2) Abrupt withdrawal of treatment with Tramadol ( Generic Ultram ), even at the recommended dose, can induce withdrawal symptoms. (3) In practice, patients must be advised to stop their treatment gradually, especially after lengthy treatment periods. Prescription renewals are a good opportunity to re-assess the need for Tramadol ( Generic Ultram ). Use of this opioid analgesic should not be trivialised.