Tapentadol is a m-opioid receptor (MOR) agonist and norepinephrine reuptake inhibitor (NRI) with established efficacy in neuropathic pain in patients and intrinsic synergistic interaction of both mechanisms as demonstrated in rodents. In diabetic mice, we analyzed the central antihyperalgesic activity, the occurrence of site-site interaction, as well as the spinal contribution of opioid and nor...

The purpose of the present study was to characterise Ca2+ currents in smooth muscle cells isolated from biopsy samples taken from the proximal urethra of patients undergoing surgery for bladder or prostate cancer. Cells were studied at 37 degrees C using the amphotericin B perforated-patch configuration of the patch-clamp technique. Currents were recorded using Cs+-rich pipette solutions to blo...

UNLABELLED (11)C-LY2795050 is a novel κ-selective antagonist PET tracer. The in vitro binding affinities (Ki) of LY2795050 at the κ-opioid (KOR) and μ-opioid (MOR) receptors are 0.72 and 25.8 nM, respectively. Thus, the in vitro KOR/MOR binding selectivity is about 36:1. Our goal in this study was to determine the in vivo selectivity of this new KOR antagonist tracer in the monkey. METHODS To...

PURPOSE The bradycardia produced by pyridostigmine and physostigmine in an animal model of acute cardiac denervation was examined according to its relation to cholinesterase inhibition and sensitivity to block by cholinergic receptor antagonists. METHODS Cats were anaesthetised, vagotomised and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of a...

BACKGROUND Combining different analgesic drugs for improvement of drug efficacy is a recommended strategy intended to achieve the optimal therapeutic effects. OBJECTIVES The purpose of the present study was to assess the nature of the interaction between ascorbic acid and two analgesic drugs, morphine and tramadol. MATERIALS AND METHODS The analgesic activity was assessed by the acetic acid...

The mechanisms of Ca(2+)-induced mucin secretion were examined in monolayers of the differentiated epithelial colon cell line C1.16E by combined measurements of free intracellular Ca2+ ([Ca2+]i) using a fluorescence indicator and mucous secretion using a specific and sensitive electrophoretic assay. Carbachol, a cholinergic agonist, induced an initial concentration-dependent [Ca2+]i peak increa...

Avibactam is a novel non-β-lactam β-lactamase inhibitor that has been shown in vitro to inhibit class A, class C, and some class D β-lactamases. It is currently in phase 3 of clinical development in combination with ceftazidime. In this study, the efficacy of ceftazidime-avibactam was evaluated in a murine septicemia model against five ceftazidime-susceptible (MICs of 0.06 to 0.25 μg/ml) and 15...

The ability of tiapride, a selective D2/D3 dopamine receptor antagonist, to exert discriminative stimulus control of responding was investigated by training rats to discriminate this drug (30 mg/kg) from saline in a two-lever, food-reinforcement procedure. Acquisition of tiapride discrimination required a relatively lengthy training period (mean of 76 sessions) but stable performance was mainta...

We have noted previously that duration of vecuronium block correlated with fibre size in six muscle groups in the goat. Electrophysiological considerations suggest that the important factor should be the number of acetylcholine receptors (AChR) relative to fibre size. However, this hypothesis could not be verified in the goat because the number of AChR was relatively constant in the different m...