Pharmacology
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Anesthesia, a state of profound central nervous system suppression, involves a sequence of events that is still not well understood. In the present study, we examined the action of propofol (a sedative-hypnotic drug commonly used as anesthetic) on thalamocortical functional connectivity in rats by using functional connectivity magnetic resonance imaging (fcMRI) with a 3.0-tesla MR scanner. Intraperitoneal injections of propofol (80 or 160 mg/kg) were administered to Sprague-Dawley rats. ⋯ These observations indicate that thalamocortical connectivity may play an important role in propofol anesthesia. We also observed that regionally specific long-range correlations of spontaneous low-frequency physiological fluctuations in BOLD signals may be present across somatosensory networks of the brain in the absence of external stimulation. However, our experiment suggests that fcMRI can be used to investigate brain networks that exhibit correlated fluctuations.
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Progesterone has been shown to play a role in pain perception. However, the effects of progesterone on P2X3 receptors, the nociception-related receptors in primary sensory neurons, remain unclear. ⋯ These results suggest that progesterone may modulate pain signal transmission on dorsal root ganglia via regulating P2X3 receptor function. The cAMP-PKA signaling pathway is involved in the downregulating effect of progesterone on P2X3 receptors.
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Sevoflurane is widely used for anesthesia, and is commonly used together with opioids in clinical practice. However, the effects of sevoflurane on μ-opioid receptor (μOR) functions is still unclear. In this study, the effects of sevoflurane on μOR functions were analyzed by using Xenopus oocytes expressing a μOR fused to chimeric Gα protein G(qi5) (μOR-G(qi5)). ⋯ The inhibitory effects of sevoflurane on the DAMGO-induced currents were not observed in oocytes pretreated with the protein kinase C (PKC) inhibitor GF109203X. These findings suggest that sevoflurane would inhibit μOR function. Further, the mechanism of inhibition by sevoflurane would be mediated by PKC.
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The present study was designed to investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (atorvastatin, pravastatin, simvastatin) on the pharmacokinetics of losartan and its active metabolite EXP-3174 in rats. Pharmacokinetic parameters of losartan and EXP-3174 in rats were determined after oral and intravenous administration of losartan (9 mg/kg) without and with HMG-CoA reductase inhibitors (1 mg/kg). The effect of HMG-CoA reductase inhibitors on P-gp and cytochrome (CYP) 3A4 activity were also evaluated. ⋯ Consequently, the absolute bioavailability (F) of losartan after oral administration with simvastatin was significantly increased by 59.4% compared to that of control. The metabolite-parent AUC ratio was significantly decreased by 25.7%, suggesting that metabolism of losartan was inhibited by simvastatin. In conclusion, the enhanced bioavailability of losartan might be mainly due to inhibition of P-gp in the small intestine and CYP3A subfamily-mediated metabolism of losartan in the small intestine and/or liver and to reduction of the CL/F of losartan by simvastatin.
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Randomized Controlled Trial
Co-administration of ondansetron decreases the analgesic efficacy of tramadol in humans.
Tramadol, a central analgesic acting on serotonin neurotransmission, is often co-used with ondansetron, a 5-HT(3) antagonist, for the management of postoperative pain to decrease nausea and vomiting. The aim of the study is to test the hypothesis that this drug combination raises tramadol requirement by patient-controlled analgesia (PCA). ⋯ Tramadol consumption (mg × kg(-1) × h(-1)) was higher in the ondansetron group at the 2-hour time point compared to the control group (0.24 ± 0.1 vs. 0.17 ± 0.16; p = 0.01). Our study suggests that ondansetron acutely reduces the analgesic efficacy of tramadol.