Naunyn-Schmiedeberg's archives of pharmacology
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Naunyn Schmiedebergs Arch. Pharmacol. · Jun 2010
Reduction of ICAM-1 expression by carbon monoxide via soluble guanylate cyclase activation accounts for modulation of neutrophil migration.
Previously, it was demonstrated that the heme/heme oxygenase (HO)/carbon monoxide (CO) pathway inhibits neutrophil recruitment during the inflammatory response. Herein, we addressed whether the inhibitory effect of the HO pathway on neutrophil adhesion and migration involves the reduction of intracellular adhesion molecule type (ICAM)-1 and beta(2)-integrin expression. Mice pretreated with a specific inhibitor of inducible HO (HO-1), zinc protoporphyrin (ZnPP) IX, exhibit enhanced neutrophil adhesion and migration induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). ⋯ Finally, it was observed that the nitric oxide (NO) anti-inflammatory effects on ICAM-1 expression appear to be indirectly mediated by HO-1 activation, since the inhibition of HO-1 prevented the inhibitory effect of the NO donor (S-nitroso-N-acetylpenicillamine) on LPS-induced ICAM-1 expression. Taken together, these results suggest that CO inhibits ICAM-1 expression on endothelium by a mechanism dependent on sGC activation. Thus, our findings identify the HO-1/CO/guanosine 3'5'-cyclic monophosphate pathway as a potential target for the development of novel pharmacotherapy to control neutrophil migration in inflammatory diseases.
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Naunyn Schmiedebergs Arch. Pharmacol. · Feb 2010
Randomized Controlled TrialAbsorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery--a pilot study.
The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. ⋯ Individual CSF lag times with respect to (50%) peak plasma concentration were
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Naunyn Schmiedebergs Arch. Pharmacol. · Dec 2009
Comparative StudyPharmacological profile of intrathecal fadolmidine, a alpha2-adrenoceptor agonist, in rodent models.
The present experiments compared the peripheral and central pharmacological effects of three alpha(2)-adrenoceptor agonists: fadolmidine, clonidine, and dexmedetomidine after single intrathecal bolus injections at analgesic dose level in rats. Effects on mydriasis and cardiovascular functions were studied in anaesthetised rats, the effects on sedation/motor performance, body temperature, and gastrointestinal motility were evaluated in conscious rats, and also the effects on brain biogenic amines were studied. ⋯ The difference in the systemic effect profile between fadolmidine and clonidine or dexmedetomidine is most probably explained by differences in their ability to spread from the site of administration at the lumbar level into the periphery and/or the brain and further the concentrations of the compounds in the side of action. These results supports that intrathecally administered fadolmidine could have potential to be used as an analgesic agent with less subraspinal or spinal adverse effects at analgesic doses than dexmedetomidine and clonidine.
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Naunyn Schmiedebergs Arch. Pharmacol. · Nov 2009
Magnesium modifies fentanyl-induced local antinociception and hyperalgesia.
Fentanyl-induced hyperalgesia and antinociception after systemic administration has been shown in previous clinical and experimental studies. However, there is very little evidence regarding the local possible effects of fentanyl. The purpose of this study was to assess whether local (intraplantar) fentanyl administration can produce antinociception and hyperalgesia. ⋯ In the presence of magnesium, hyperalgesia after fentanyl administration was not observed. Consequently, following the fentanyl administration, local hyperalgesia after antinociception is a negative effect in pain treatment. Magnesium may not only prevent the hyperalgesia but also enhance antinociceptive effect of fentanyl.
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Naunyn Schmiedebergs Arch. Pharmacol. · Oct 2009
The peripheral administration of a nitric oxide donor potentiates the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice.
Several works reveal that nitric oxide could enhance the peripheral antinociception induced by opioids during acute inflammation. Nonetheless, the role of nitric oxide in the local antinociceptive effects of delta-opioid receptor (DOR) agonists during chronic peripheral inflammation is not known. The aim of this study is to evaluate whether nitric oxide would enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice. ⋯ Moreover, the co-administration of NOC-18 with DPDPE significantly increased the antinociceptive effects produced by DPDPE from 1 to 10 days of CFA-induced inflammatory pain (P < 0.05). These effects were completely blocked by naltrindole and naloxone methiodide. Our results demonstrate that nitric oxide might enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain by interaction with peripheral DOR, representing a useful strategy for an efficient antinociceptive treatment of peripheral inflammatory pain.