Methods and findings in experimental and clinical pharmacology
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Methods Find Exp Clin Pharmacol · Jan 2010
Comparative StudySimilar and different effects of capsaicin and resiniferatoxin on substance P release and transient receptor potential vanilloid type 1 expression of cultured rat dorsal root ganglion neurons.
The purpose of this study was to investigate the effects of capsaicin (CAP) and resiniferatoxin (RTX) on substance P (SP) release and transient receptor potential vanilloid type 1 (TRPV1) expression of cultured rat dorsal root ganglion (DRG) neurons. Dissociated DRG cells of embryonic 15-day-old Wistar rat were cultured for 3 days and then exposed to CAP (1 micromol/L, 10 micromol/L) or RTX (10 nmol/L, 100 nmol/L) for 10 min. At 3 days of culture growth, SP release increased significantly after 10 min of stimulation with CAP or RTX as compared with controls. ⋯ Preprotachykinin (PPT) mRNA, TRPV1 mRNA and TRPV1 protein expression decreased in CAP-treated cultures and RTX cultures treated with the higher concentration, whereas RTX cultures treated with the lower concentration were not affected. The results indicate that CAP and high concentrations of RTX are more neurotoxic to cultured rat DRG neurons while the inability of the neurons to express SP or TRPV1 after acute exposure to the lower concentration of RTX could be partially reversed after a period of incubation. The efficacy and therapeutic potential of the reversible action of RTX are more applicable as strategies for pain or neurogenic inflammation therapy.
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Methods Find Exp Clin Pharmacol · Jan 2010
Clinical TrialIn vitro and in vivo characterization of tapentadol metabolites.
Tapentadol is a novel, centrally acting analgesic combining micro-opioid receptor (MOR) agonism and noradrenaline (NA) reuptake inhibition in a single molecule. Many classic opioids form active metabolites that contribute to analgesia and/or side effects, and the involved cytochrome P450 enzyme complex can give rise to pharmacokinetic drug-drug interactions and variability in drug efficacy due to enzyme polymorphisms. Here we report on the relevance of tapentadol metabolites. ⋯ The absence or presence of analgesia correlated with moderate activity (0.5 microM < K(i) < 1.1 microM) at the NA transporter or MOR. However, the systemic exposure for these metabolites found in humans after therapeutic oral doses of tapentadol was far below their respective K(i) values at these binding sites (by a factor of > 45). Thus, it is highly unlikely that tapentadol forms metabolites that contribute in any relevant degree to its analgesic activity.
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Methods Find Exp Clin Pharmacol · Oct 2009
Comparative StudyPostmarketing cohort study to assess the safety profile of oral dexketoprofen trometamol for mild to moderate acute pain treatment in primary care.
Recently, new concerns on the safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) have been raised by the European Medicines Agency (EMEA) and other regulatory authorities. The safety profile of oral dexketoprofen trometamol for the treatment of acute mild to moderate pain of different causes in actual conditions of use in the primary care setting was assessed. A prospective cohort study was designed to evaluate the tolerability of dexketoprofen compared with other commonly prescribed analgesics. ⋯ Risks for gastrointestinal AEs were adjusted for age, gender, history of previous NSAID intake, gastroprotective drugs and reason for prescription. Taking metamizole-paracetamol as the reference group, the odds ratios (OR, 95%) were: 1.30 (0.77-2.19) for dexketoprofen, 1.57 (0.79-3.13) for ibuprofen and dexibuprofen, 2.31 (0.64-8.27) for naproxen, 2.63 (0.85-8.15) for piroxicam and 3.37 (1.87-6.06) for aceclofenac-diclofenac. These results confirm the safety of oral treatment with dexketoprofen in patients with acute pain of various etiologies observed in previous studies and support the use of dexketoprofen as a first-line drug for the approved therapeutic indications.
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Methods Find Exp Clin Pharmacol · Jun 2009
Randomized Controlled TrialDexamethasone for the reduction of postoperative nausea and vomiting and analgesic requirements after middle ear surgery in adult Japanese patients.
A prospective, randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy of dexamethasone for reducing postoperative nausea and vomiting (PONV) and analgesic requirements after middle ear surgery. Adult Japanese patients were allocated randomly to 1 of 3 groups (n = 30 each) to receive either placebo or dexamethasone at 2 different doses (4 mg and 8 mg) immediately before induction of anesthesia. Postoperatively, emetic episodes and analgesic requirements were evaluated by a blinded investigator. ⋯ No difference in analgesic requirement was found between the dexamethasone 4 mg and placebo groups (P = 0.396). No clinically important adverse events attributable to the study drug were observed in any of the groups. In conclusion, dexamethasone 8 mg is effective in reducing the rate of PONV and analgesic requirements in adult Japanese patients undergoing middle ear surgery.
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Methods Find Exp Clin Pharmacol · Apr 2009
Comparative Study Clinical TrialEfficacy and safety of oral citicoline in acute ischemic stroke: drug surveillance study in 4,191 cases.
Citicoline is an essential precursor in the synthesis of phosphatidylcholine, a key cell membrane phospholipid, and is known to have neuroprotective effects in acute ischemic stroke. The aim of this study was to determine the efficacy and safety of oral citicoline in Korean patients with acute ischemic stroke. A drug surveillance study was carried out in 4,191 patients with a diagnosis of acute ischemic stroke. ⋯ Citicoline safety was excellent; 37 side effects were observed in 31 patients (0.73%). The most frequent findings were nervous system-related symptoms (8 of 37, 21.62%), followed by gastrointestinal symptoms (5 of 37, 13.5%). Oral citicoline improved neurological, functional and global outcomes in patients with acute ischemic stroke without significant safety concerns.