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The central-acting analgetic (Tramadol ( Generic Ultram ) 50 mg) demonstrated significant effects on wave latencies of provoked potentials in females. However, the same doze had no significant effect on wave latencies of provoked potentials in males. Tramadol ( Generic Ultram ) provoked a statistically significant reduction of all wave amplitudes of provoked potentials of dental pulp in both sexes. Thus, provoked potentials recorded under this condition gave an "objective" index of Tramadol ( Generic Ultram ) analgetic effects.
 Involvement of potassium channels and nitric oxide in Tramadol ( Generic Ultram ) antinociception. It has been considered that Tramadol ( Generic Ultram ), a centrally acting analgesic, shows its effect via opiatergic, noradrenergic, and serotonergic systems. It has a low affinity for opioid receptors, and its effect can be partly blocked by naloxone. Since the noradrenergic and serotonergic mechanisms are still unknown, other systems which are associated with pain and analgesia may have a role on the antinociceptive effect of Tramadol ( Generic Ultram ). The aim of this study was to evaluate the effects of K(+) channels and nitrergic systems on the antinociceptive action of Tramadol ( Generic Ultram ). The antinociceptive effects of Tramadol ( Generic Ultram ) were determined in mice by the hot plate test. To examine the effects of K(+) channels and the nitrergic system nonspecific voltage-dependent K(+) channel blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA), nitric oxide (NO) precursor l-arginine, and the NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) were used. Our results indicated that 4-AP, TEA, and l-arginine reduced the antinociceptive effect of Tramadol ( Generic Ultram ). However, l-NAME augmented the antinociceptive effect of Tramadol ( Generic Ultram ). The reduction of the effects of Tramadol ( Generic Ultram ) by l-arginine was reversed by l-NAME. The results of our study suggest that nonspecific voltage-dependent K(+) channels and nitrergic system have a role on the antinociceptive effect of Tramadol ( Generic Ultram ) in mice hot plate test.
 Use of Tramadol ( Generic Ultram ) versus pethidine versus denaverine suppositories in labor--a contribution to noninvasive therapy of labor pain Because Tramadol ( Generic Ultram ) does not exhibit an depressive effect on ventilatory activity it is often be used in the obstetrical analgesia, at most in form of an intramuscularly injection. In a prospective study on at all 49 women under labour the clinical effect of the noninvasive rectal application of Tramadol ( Generic Ultram ), Pethidin, and Denaverin has been compared. The first dosage was 100 mg of all substances. Around the half of the women said that analgetic effect was good or very good. On only every fifth it was sufficient or not enough. The effect was at near the same in all treatment groups. Because of a low incidence of maternal side effects, the absence of side effects on the newborn, and near the same results on the analgetic effect of parenteral application in other studies, Tramadol ( Generic Ultram ) suppositories can be recommended for obstetrical analgesia. 
 Actions of drugs affecting the cough reflex BACKGROUND AND AIM: Authors evaluated the part of some receptor systems in the antitussive activity of drugs. METHOD: The cough was induced by mechanical stimulation of the airways. Unanesthetized cats were used in this study. RESULTS: They followed: 1. statistically highly significant decrease of cough parameters after administration the drugs influencing the different types of opiate receptors--Tramadol ( Generic Ultram ), tilidine, pentazocine, codeine and butorphanol. Every of these drugs were administered in a dose 10 mg/kg b.w. intraperitoneally, 2. the antitussive activity of codeine was decreased by pretreatment with naloxone only in part, 3. selective antagonist 5-HT2 receptors ketanserine (1 mg/kg b.w.) decreased antitussive effect of codeine by 10% and effect of Tramadol ( Generic Ultram ) by 20%, 4. the ability of codeine to reduce the cough parameters was unchanged after pretreatment with haloperidol (0.1 mg/kg b.w.), 5. whereas the pretreatment with reserpine decreased the cough-suppressing effect of codeine, 6. the application of gabaergic agent gabalid leads to the highly significant decrease the cough parameters. Results of these experiments showed that gaba-ergic mechanism might be involved in the mechanism of action of narcotic antitussives agents, 7. we showed, that inhibition of glutaminergic synaptic transmissions afferent impulses from cough receptors with dextromethorphan leads to suppressing cough reflex in cats. CONCLUSIONS: Antitussive activity of agents is not only mediated by means of mi opiate receptors. The results suggest, that gabaergic, serotoninergic systems and activity of NMDA receptors play an important role in the mechanism of action of antitussive drugs. Decrease in levels of brain monoamines modifies the cough-depressant effect of codeine. (Fig. 7, Ref. 23.)
 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.
 How we use opioid drugs on patients with neoplasms Tramadol ( Generic Ultram ) is a centrally acting analgesic drug with a dual mechanism of action: binding to mu-opioid receptors and potentiation of the monoaminergic systems. In this study, we evaluated the effects of the acute and chronic administration of Tramadol ( Generic Ultram ) on nociceptive thresholds (by the hot-plate test) and on immune responses (by measuring Concanavalin A-induced splenocyte proliferation, IL-2 production and natural killer activity) in the mouse. After acute subcutaneous administration, Tramadol ( Generic Ultram ) induced antinociception starting from a dose of 20 mg/kg, whereas it significantly enhanced natural killer activity and IL-2 production at doses as low as 1 mg/kg and splenocyte proliferation starting from a dose of 10 mg/kg. After the chronic administration, the antinociceptive effect of the drug was still present, whereas the immune modifications disappeared. Thus, the pharmacological profile of Tramadol ( Generic Ultram ) is totally different from that of other drugs which bind mu-opioid receptors. Our results suggest that Tramadol ( Generic Ultram ) could be a good choice for the treatment of pain in patients where immunosuppression may be particularly contraindicated.
 Based on the recent finding that Tramadol ( Generic Ultram ) (TRAM) produces conditioned place preference (CPP) and dopamine release in the nucleus accumbens, it was suggested that the abuse liability of TRAM may be greater than hitherto assumed. We re-evaluated the effects of TRAM in CPP and behavioral sensitization, in comparison with morphine (MOR) and meptazinol (MEPT), an opioid drug with minimal abuse potential. While MOR produced CPP and very strong locomotor sensitization, TRAM and MEPT produced only CPP. It has been suggested that sensitization plays an important role in the development of addiction, hence our results suggest that the abuse potential of TRAM might resemble more that of MEPT than that of MOR, and they are consistent with the clinical picture, in that although TRAM is not completely devoid of positively reinforcing effects, reports on abuse are rare. The low propensity to induce addiction may be related to the lack of changes in the brain circuitry mediating reward and motivation, as evidenced by the lack of sensitization. Copyright 2002 Elsevier Science Ireland Ltd.
 Withdrawal characteristics following frequent intravenous administration of several opioids in rats Characteristics of withdrawal signs of several opioids were compared in rats after short-term frequent intravenous infusions. Male Sprague-Dawley rats with catheters implanted in the jugular veins were infused with a fixed dose of a drug hourly for 72 hrs. Thirty min after the final infusion, naloxone 4 mg/kg, s.c. was administered and withdrawal signs were observed for 1 hr and the severity of the withdrawal signs was scored, classified into a behavioral sign score, autonomic sign score, and body weight loss score. As a result, total withdrawal scores of morphine, methadone, d-propoxyphene, loperamide, Tramadol ( Generic Ultram ), and pentazocine were significantly higher than that of saline, with the highest score being observed for 4 mg/kg or more of morphine. The total score of ethylketocyclazocine was slightly but significantly higher than that of saline. Buprenorphine and thebaine produced no observable withdrawal signs. The behavioral sign score tended to be higher than the other 2 scores in the drugs showing relatively low but significant total scores such as Tramadol ( Generic Ultram ), pentazocine, and ethylketocyclazocine, while the score of autonomic signs or the body weight loss tended to be higher in drugs showing high total scores. Thus, in the case of opioids, it is considered that the severity of withdrawal signs was mainly derived from the autonomic signs including diarrhea which may result in body weight loss. 
 The antinociceptive activity of flupirtine: a structurally new analgesic. The antinociceptive activity of flupirtine was measured in various test procedures predictive of analgesic activity. In the electrostimulated pain test in mice the oral ED50 for flupirtine was 25.7 mg/kg p.o. Thus, flupirtine was approximately 31.7 times more potent than paracetamol (ED50: 814 mg/kg p.o.) and as potent as pentazocine (ED50: 38.5 mg/kg p.o.). Morphine (ED50: 16.8 mg/kg p.o.) was 1.5 times and buprenorphine (ED50: 2.6 mg/kg p.o.) 9.9 times more potent than flupirtine. In the hot plate test (mice) flupirtine (ED50: 32 mg/kg p.o.) was approximately half as potent as morphine (ED50: 15.5 mg/kg p.o.). The oral and intravenous antinociceptive activity (ED50) of flupirtine in the electrical tooth pulp stimulation test in conscious dogs was 3.5 mg/kg p.o. and 0.7 mg/kg i.v. which was similar to that of pentazocine (ED50: 4.2 mg/kg p.o. and 0.5 mg/kg i.v.). Buprenorphine had, as expected, stronger antinociceptive activity (ED50: 1.0 mg/kg p.o. and 0.04 mg/kg i.v.). Fifteen minutes after oral administration of 40 mg/kg flupirtine, the pain threshold in the electrostimulated pain test was increased by 54%. The maximal antinociceptive effect was observed 30 minutes after dosing. The analgesia lasted at least 75 minutes. Codeine significantly elevated the pain threshold 15 minutes after dosing. Its maximal effect was also reached 30 min after application but the antinociceptive activity wore off earlier than after flupirtine. The intracerebroventricular and intrathecal administration of flupirtine also caused dose dependent antinociceptive activity in dose ranges which, when applied systematically, did not produce analgesia in rats. The antinociceptive activity of flupirtine was not abolished by naloxone whether given orally or by the intraventricular or intrathecal routes. In opiate receptor binding studies flupirtine had no affinity for mu, delta or kappa opiate receptors at the highest concentration used (10(-5) M). Whereas buprenorphine and Tramadol ( Generic Ultram ) showed a striking similarity in the pharmaco-electroencephalogram recorded from different parts of the brain (frontal cortex, thalamus, striatum and the mesencephalic reticular formation) of the freely moving rat, flupirtine was clearly different in action. It produced dose dependent increases in nearly all frequency bands but its effects were different from those of the minor tranquillizer diazepam and the anticonvulsant phenobarbitone. These findings show that the central antinociceptive activity of flupirtine is not based on an opiate mechanism and is not comparable with that of diazepam and phenobarbitone.
 Opioid use by patients in an orthopedics spine clinic.Mahowald ML, Singh JA, Majeski P.Minneapolis VAMC, and the University of Minnesota, Minneapolis.OBJECTIVE: Concerns regarding the efficacy, toxicity, tolerance, dependence, and abuse of opioids have limited their use for patients with chronic spine pain. In our previous study of rheumatology clinic patients, opioid analgesics were found to be highly effective, produced only mild side effects, and had few instances of opioid abuse. The purpose of this study was to replicate our previous study in another large cohort of patients with nonmalignant pain due to well-defined spinal diseases. METHODS: Opioid use was studied in 230 orthopedics spine clinic patients by retrospective analysis of prescriptions for 3 years and cross-sectional analysis of efficacy and toxicity by patient interviews. Opioid use and stability of the daily dose over 3 years were derived from computerized pharmacy records. Medical records, operative reports, and radiographic studies were reviewed to determine the reason for dosage escalations and to detect instances of abuse or addiction behaviors. Patients were interviewed to determine the efficacy, frequency, and types of side effects and instances of obtaining opioids from sources outside the Veterans Affairs system. RESULTS: Opioids were prescribed for 152 of the 230 patients, for <3 months (short-term [STO]) in 94, >/=3 months (long-term [LTO]) in 58, and none in 72 (no opioid [NTO]). Medications prescribed were codeine, oxycodone, propoxyphene, Tramadol ( Generic Ultram ), morphine, meperidine, fentanyl, or hydroxycodone, either alone or in combination. Interviews were completed in 72 STO, 50 LTO, and 45 NTO patients. Pain severity (0-10 scale) was not different in patients with different spinal pathologies. Opioids significantly reduced the back pain severity score from 8.3 +/- 1.5 to 4.5 +/- 2.2 (mean +/- SD). Mild side effects (most commonly, constipation and sedation) were reported by