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.

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.




Effect of droperidol and Tramadol ( Generic Ultram ) combination on the hemostasis in rabbits

The effect of a combined administration of analgesic droperidol and neuroleptic Tramadol ( Generic Ultram ) (tramal) on the plasma coagulation and platelet aggregation was studied on awake rabbits. Both Tramadol ( Generic Ultram ) and droperidol, as well as their combination, enhance the coagulation of plasma proteins and suppress the thrombocyte deaggregation process.


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.

Effects of Tramadol ( Generic Ultram ) on alpha2-adrenergic receptors in the rat brain.Faron-Gorecka A, Kusmider M, Inan SY, Siwanowicz J, Dziedzicka-Wasylewska M.Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Cracow PL-31-343, Poland.In recent years, it has been postulated that Tramadol ( Generic Ultram ), used mainly for the treatment of moderate to severe pain, might display a potential as an antidepressant drug. The present study investigated the effects of acute and repeated Tramadol ( Generic Ultram ) administration on the binding of [3H]RX 821002, a selective alpha2-adrenergic receptor ligand, in the rat brain. Male Wistar rats were used. Tramadol ( Generic Ultram ) (20 mg/kg, i.p.) administered acutely (single dose), at 24 h after dosing, induced a significant decrease in the alpha2-adrenergic receptors in all brain regions studied. The most pronounced effects were observed in all subregions of the olfactory system, nucleus accumbens and septum, thalamus, hypothalamus, amygdala, and cerebral cortex. Repeated treatment with Tramadol ( Generic Ultram ) (20 mg/kg, i.p., once daily for 21 days) also induced statistically significant downregulation of [3H]RX 821002 binding sites in the rat brain. However, the effect--although statistically significant--was less pronounced than in the group treated acutely with the drug. Since drugs such as mianserin and mirtazapine are potent antagonists of central alpha2-adrenergic receptors and are effective antidepressants, it is tempting to suggest that, in addition to other alterations induced by Tramadol ( Generic Ultram ), downregulation of these receptors may represent a potential antidepressant efficacy. On the other hand, one should be careful to avoid the treatment of chronic pain with Tramadol ( Generic Ultram ) in patients already receiving antidepressant drugs. Tramadol ( Generic Ultram )-induced downregulation of alpha2-adrenergic receptors--when combined with ongoing antidepressant therapy with drugs, which themselves inhibit serotonin reuptake or are antagonists of alpha2-adrenergic receptors--might cause threatening complications.