Effect of combined treatment with mirtazapine and risperidone on the MK-801-induced changes in the object recognition test in mice.
To investigate the effect of a combination of acid-suppressing and prokinetic drugs or eradication therapy on the course of H. pylori-positive FD.
Among the treatments proposed in the literature for cancer-related cachexia, some proved to be ineffective, namely, cyproheptadine, hydrazine, metoclopramide, and pentoxifylline. Among effective treatments, progestagens are currently considered the best available treatment option for cancer-related cachexia, and they are the only drugs approved in Europe. Drugs with a strong rationale that have failed or have not shown univocal results in clinical trials so far include eicosapentaenoic acid, cannabinoids, bortezomib, and anti-TNF-alpha MoAb. Several emerging drugs have shown promising results but are still under clinical investigation (thalidomide, selective cox-2 inhibitors, ghrelin mimetics, insulin, oxandrolone, and olanzapine).
Preoperative pregabalin may be a useful analgesic for patients after laparoscopic cholecystectomy, as it lowers pain intensity and opiod consumption, and does not increase the frequency of side effects.
Effects of metoclopramide and domperidone on the human α-subunit Nav1.5 expressed in human embryonic kidney 293 cells and on Na currents in neonatal rat cardiomyocytes were investigated by means of whole-cell patch clamp recordings.
There is a recently formulated hypothesis that metoclopramide (MCP) may stimulate gastrointestinal (GI) motility via an antagonistic action on presynaptic, release modulating muscarinic receptors. We have tested this hypothesis by comparing MCP and zetidoline (ZTD), another putative presynaptic muscarinic antagonist, in various GI motility assays. The muscarinic and dopamine receptor binding affinity was also measured. Both MCP and ZTD acted as stimulants of electrically induced twitches of the isolated guinea-pig ileum and as antagonists of the inhibitory effects of intermittent exposure to cholinomimetics on the same preparation. In vivo, MCP significantly accelerated GI transit in mice and gastric emptying in rats. In contrast, ZTD had no effect on these in vivo parameters. Thus MCP and ZTD seem to act on the isolated guinea-pig ileum as presynaptic muscarinic antagonists. However, this mechanism apparently does not contribute to stimulation of GI motility in vivo.
A randomized prospective clinical trial was conducted to evaluate the potential utility of adding transdermal scopolamine to a standard regimen of metoclopramide and dexamethasone for the prevention of cisplatin-induced emesis. Thirty-one patients who were about to receive their first cycle of chemotherapy, using a combination regimen including cisplatin at a dose greater than or equal to 60 mg/m2 were randomized to receive an antiemetic regimen of either metoclopramide and dexamethasone alone, or these two drugs plus transdermal scopolamine patches. The mean number of episodes of emesis was .63 +/- 1.31 in the 16 scopolamine-treated patients, and 2.27 +/- 2.66 in the 15 patients who did not receive scopolamine (P less than .01). The scopolamine appeared to inhibit extrapyramidal reactions to the metoclopramide, but the number of cases was too small for statistical significance. We conclude that the addition of transdermal scopolamine to a standard metoclopramide and dexamethasone antiemetic regimen provides additive benefit in the control of cisplatin-induced emesis.
Whole cell and patch clamp techniques were used to investigate the properties of 5-HT3 receptors of a murine neuroblastoma cell line (N1E-115) and adult rabbit nodose ganglion neurones. In addition, some preliminary results from guinea-pig nodose ganglion neurones are presented. In such cells, voltage-clamped at -60 mV, 5-HT (10 microM) induced an inward current associated with a conductance increase. The results of ion substitution experiments suggest that the 5-HT activated ion channel is permeable to both Na+ and K+ ions with a permeability ratio (PNa/PK) of 0.94 and 0.92 for rabbit nodose ganglion cells and N1E-115 cells respectively. On outside out membrane patches excised from rabbit nodose ganglion neurones, 5-HT (1 microM) activated clearly discernible single channel currents with a conductance of 16.6 +/- 0.7 pS (n = 4). In contrast, fluctuation analysis of 5-HT induced whole cell currents suggests that the single channel conductance of N1E-115 cells is only 0.3 pS, a value some 50 fold lower. The 5-HT-induced whole cell currents recorded from all three preparations were antagonised by the selective 5-HT3 receptor antagonist ondansetron (GR38032F) and by the less selective agents metoclopramide, cocaine and (+)-tubocurarine. However, these preparations demonstrate a differential sensitivity to some antagonists. In particular, (+)-tubocurarine was a potent antagonist in N1E-115 cells (IC50 = 0.85 nM) but was approximately 200 fold (IC50 = 156 nM) and 1200 fold (IC50 = 10 microM) less potent in rabbit and guinea-pig nodose ganglion neurones respectively. Additionally, a novel effect of ketamine (10 microM) to potentiate the 5-HT-induced current of rabbit nodose ganglion neurones is described.