Effects of the central analgesic tramadol on the uptake and release of noradrenaline and dopamine in vitro.

1. The centrally acting analgesic, tramadol, has low affinity for opioid receptors and therefore presumably other mechanisms of analgesic action. Neurotransmitter release and uptake experiments were used to characterize the effects of tramadol on the central noradrenergic and dopaminergic systems.

Additional myocardial salvage by coadministration of the epoprostenol analog taprostene to recombinant single-chain urokinase-type plasminogen activator in a canine coronary thrombosis model.

In open chest dogs myocardial ischemia was induced by formation of an occlusive thrombus in the left anterior circumflex artery (LCX). Reperfusion of the LCX was achieved by infusion of the fibrin specific recombinant single-chain urokinase-type plasminogen activator (r-scu-PA). The myocardial salvage by r-scu-PA alone and in combination with the epoprostenol (prostacyclin) analog taprostene (CG 4203) was compared.

Protection by recombinant human superoxide dismutase in lethal rat endotoxemia.

In summary as mechanism of the overall protective effect of r-HSOD in lethal rat endotoxemia, inhibition of hemoconcentration, a tendency of a decreased leukocyte activation and attenuation of consumption coagulopathy could be established.

Enhanced myocardial salvage by combined treatment with recombinant single-chain urokinase-type plasminogen activator and recombinant human superoxide dismutase in a canine coronary thrombosis model.

Myocardial ischemia was induced by formation of an occlusive thrombus in the left anterior circumflex artery (LCX) in open chest dogs. The myocardial salvage by the fibrin specific recombinant single-chain urokinase-type plasminogen activator (r-scu-PA) alone and in combination with the oxygen radical scavenger human superoxide dismutase of recombinant origin (r-HSOD) was investigated. The three experimental groups were: group I (n = 4) did not receive any treatment after LCX thrombosis; in group II (n = 9) at 100 min after LCX thrombosis r-scu-PA (20 micrograms.

Equieffective protection by human and bovine SOD against renal reperfusion damage in rats.

Both hum-SOD and bov-SOD improved the impaired renal function during kidney reperfusion. In the experiments with a 60-min occlusion period the effects of bov-SOD tended to be more pronounced than the effects of hum-SOD, whereas after a 30-min occlusion period the improvement of renal function by hum-SOD was more striking. In essence, therefore, hum-SOD proved to be equipotent to bov-SOD.

Endotoxins, arachidonic acid, and superoxide formation.

The pathophysiologic relevance of altered eicosanoid metabolism and free-radical production during endotoxemia is reviewed. A direct or complement-mediated release of eicosanoids--depending on the species, the tissue, and the kind of endotoxin--has been found to be associated with endotoxemic shock. Prostacyclin appears to be partially responsible for the early decrease in blood pressure and clearly induces the sustained hypotension of endotoxemia but is irrelevant to its fatal outcome.

Selective fibrinolytic activity of recombinant non-glycosylated human pro-urokinase (single-chain urokinase-type plasminogen activator) from bacteria.

To assess their therapeutic value recombinant non-glycosylated human pro-urokinase (cPUK) and recombinant non-glycosylated human low molecular mass urokinase (cLUK) both obtained from genetically transformed bacteria were compared with respect to their thrombolytic efficacy and their potential to induce systemic plasminogen activation which impairs the coagulation system. The investigations were performed in in vitro and in vivo test systems. In vitro, both substances significantly and concentration-dependently lysed radiolabelled human thrombi in rotating loops of tubes (Chandler-loops) with equivalent efficacy.

Anaphylactoid reactions and histamine release do not occur after application of the opioid tramadol.

After an i.v. application of 100 mg tramadol in 13 healthy volunteers no change in plasma histamine concentration could be detected,( systemic anaphylactoid reactions did not occur, cutaneous reactions were not rated as anaphylactoid since itching and erythema were seen only once after tramadol whereas erythema was also observed twice after saline, blood pressure and heart rate were only very slightly and transiently elevated without any abnormalities in ECG-readings and only side effects typical for opioid therapy were observed.

Comparison of the protective effects by human and bovine superoxide dismutase against ischemia- and reperfusion-induced impairment of kidney function in anesthetized rats.

In a rat model of ischemia- and reperfusion-induced kidney damage, the protective effects of human superoxide dismutase produced by genetic technology (hum-SOD) were compared to those of bovine superoxide dismutase (bov-SOD). The intravenous infusion of hum-SOD and bov-SOD, started concomitantly with the kidney reperfusion after a 60-min (or 30-min) period of ischemia, significantly improved the renal function (inulin and p-amino-hippuric acid clearance rates) as compared to the vehicle-treated control group. In contrast, inactive apoenzyme of superoxide dismutase (Apo-SOD) did not improve the impaired renal function after the kidney reperfusion.

Clinical investigation on the development of dependence during oral therapy with tramadol.

In a multicenter study 153 in- and outpatients suffering from severe pain were treated for three weeks with capsules containing 50 mg 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol, Tramal). The daily dosage was limited to 400 mg. At the end of the third week the patients received in a randomized double-blind manner 1.

Chemical, enzymological and pharmacological equivalence of urokinases isolated from genetically transformed bacteria and human urine.

Low molecular weight urokinase (LUK), which was prepared from E. coli containing a plasmid coding for human pro-urokinase, has an amino acid sequence identical to that of LUK isolated from human urine (uLUK) but lacks the carbohydrate side chain at Asn 144 of the B chain. This chemical difference results in an altered mobility in SDS polyacrylamide gel electrophoresis and an apparently increased specific activity of the E.

[Double-blind clinical trial of tramadol capsules. First communication: Comparison with pentazocine and placebo (author's transl)].

A new administration form of tramadol (50 mg) was compared in a multicenter double-blind trial with pentazocine (50 mg) and with placebo in patients with acute pains. Each patient received a test preparation once. The preparations were available in identical capsules.