13 research outputs found
Results of prospective randomized study of local enoxaparin delivery versus systemic heparinization for NIR stent placement
Effects of tramadol on alpha(2)-adrenergic receptors in the rat brain
WOS: 000222923000015PubMed ID: 15246863In recent years, it has been postulated that tramadol, 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 administration on the binding of [H-3]RX 821002, a selective alpha(2)-adrenergic receptor ligand, in the rat brain. Male Wistar rats were used. Tramadol (20 mg/kg, i.p.) administered acutely (single dose), at 24 h after dosing, induced a significant decrease in the alpha(2)-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 (20 mg/kg, i.p., once daily for 21 days) also induced statistically significant downregulation of [H-3]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 alpha(2)-adrenergic receptors and are effective antidepressants, it is tempting to suggest that, in addition to other alterations induced by tramadol, 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 in patients already receiving antidepressant drugs. Tramadol-induced downregulation Of alpha(2)-adrenergic receptors-when combined with ongoing antidepressant therapy with drugs, which themselves inhibit serotonin reuptake or are antagonists of alpha(2)-adrenergic receptors-might cause threatening complications. (C) 2004 Elsevier B.V. All rights reserved
Some neurochemical effects of tramadol in the rat brain resemble the effects of antidepressant drugs
17th Congress of the European-College-of-Neuropsychopharmacology -- OCT 09-13, 2004 -- Stockholm, SWEDENWOS: 000225460400138鈥uropean Coll Neuropsychopharmaco
Long-term exposure of rats to tramadol alters brain dopamine and alpha(1)-adrenoceptor function that may be related to antidepressant potency
WOS: 000224448600013PubMed ID: 15464068The aim of the present study was to determine whether tramadol, which has a potential antidepressant efficacy, evokes, when administered repeatedly, changes similar to the alterations induced by conventional antidepressant drugs. Repeated administration of tramadol (20 mg/kg i.p. for 21 days) enhanced the D-amphetamine-induced locomotor hyperactivity and increased the density of alpha(1)-adrenoceptors in the rat brain cortex, as measured by saturation analysis of [H-3]prazosin binding. Autoradiographic analysis of [H-3]7-OH-DPAT ANF [H-3]raclopride binding revealed a significant up-regulation of dopamine D2 and D3 receptors in the rat nucleus accumbens upon repeated treatment with tramadol. All the above-mentioned effects induced by repeated administration of tramadol resemble the effects induced by conventional antidepressants. However, tramadol when administered repeatedly did not increase the levels of mRNA encoding for brain-derived neurotrophic factor (BDNF) and its receptor, TrkB. This is what differs tramadol from conventional antidepressants, since neurotrophic effects of these drugs have recently been postulated. (C) 2004 Elsevier B.V. All rights reserved
Effects of tramadol on ?2-adrenergic receptors in the rat brain
PubMedID: 15246863In recent years, it has been postulated that tramadol, 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 administration on the binding of [3H]RX 821002, a selective ?2-adrenergic receptor ligand, in the rat brain. Male Wistar rats were used. Tramadol (20 mg/kg, i.p.) administered acutely (single dose), at 24 h after dosing, induced a significant decrease in the ?2-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 (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 ?2-adrenergic receptors and are effective antidepressants, it is tempting to suggest that, in addition to other alterations induced by tramadol, 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 in patients already receiving antidepressant drugs. Tramadol-induced downregulation of ?2-adrenergic receptors - when combined with ongoing antidepressant therapy with drugs, which themselves inhibit serotonin reuptake or are antagonists of ?2-adrenergic receptors - might cause threatening complications. 漏 2004 Elsevier B.V. All rights reserved.This work was supported by the statutory activity of the Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences (Krak贸w, Poland)
Long-term exposure of rats to tramadol alters brain dopamine and ? 1-adrenoceptor function that may be related to antidepressant potency
PubMedID: 15464068The aim of the present study was to determine whether tramadol, which has a potential antidepressant efficacy, evokes, when administered repeatedly, changes similar to the alterations induced by conventional antidepressant drugs. Repeated administration of tramadol (20 mg/kg i.p. for 21 days) enhanced the d-amphetamine-induced locomotor hyperactivity and increased the density of ? 1-adrenoceptors in the rat brain cortex, as measured by saturation analysis of [ 3H]prazosin binding. Autoradiographic analysis of [ 3H]7-OH-DPAT and [ 3H]raclopride binding revealed a significant up-regulation of dopamine D2 and D3 receptors in the rat nucleus accumbens upon repeated treatment with tramadol. All the above-mentioned effects induced by repeated administration of tramadol resemble the effects induced by conventional antidepressants. However, tramadol when administered repeatedly did not increase the levels of mRNA encoding for brain-derived neurotrophic factor (BDNF) and its receptor, TrkB. This is what differs tramadol from conventional antidepressants, since neurotrophic effects of these drugs have recently been postulated. 漏 2004 Elsevier B.V. All rights reserved.This work was supported by statutory activity of the Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krak贸w, Poland
Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2
The target of rapamycin (TOR) kinase assembles into two distinct multiprotein complexes, conserved across eukaryote evolution. In contrast to TOR complex 1 (TORC1), TORC2 kinase activity is not inhibited by the macrolide rapamycin. Here, we present the structure of Saccharomyces cerevisiae TORC2 determined by electron cryo-microscopy. TORC2 contains six subunits assembling into a 1.4鈥塎Da rhombohedron. Tor2 and Lst8 form the common core of both TOR complexes. Avo3/Rictor is unique to TORC2, but interacts with the same HEAT repeats of Tor2 that are engaged by Kog1/Raptor in mammalian TORC1, explaining the mutual exclusivity of these two proteins. Density, which we conclude is Avo3, occludes the FKBP12-rapamycin-binding site of Tor2's FRB domain rendering TORC2 rapamycin insensitive and recessing the kinase active site. Although mobile, Avo1/hSin1 further restricts access to the active site as its conserved-region-in-the-middle (CRIM) domain is positioned along an edge of the TORC2 active-site-cleft, consistent with a role for CRIM in substrate recruitment