Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Apr 2012
Randomized Controlled Trial Comparative StudyLack of effect of central nervous system-active doses of nabilone on capsaicin-induced pain and hyperalgesia.
The aim of the present study was to investigate the effects of nabilone on capsaicin-induced pain and hyperalgesia, as well as on biomarkers of cannabinoid central nervous system (CNS) effects. A randomized, double-blind, placebo-controlled, crossover study was conducted in 30 healthy male volunteers receiving single doses of nabilone (1, 2 or 3 mg). Pain intensity after intradermal capsaicin injections in the forearm was assessed by continuous visual analogue scale (0-100 mm). ⋯ Adverse events (AE) were common on nabilone treatment. Four subjects withdrew due to pronounced CNS AE (anxiety, agitation, altered perception, impaired consciousness). Although nabilone had marked CNS effects, no analgesic or antihyperalgesic effects were observed.
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Clin. Exp. Pharmacol. Physiol. · Jan 2012
Protective effect of ligustrazine against myocardial ischaemia reperfusion in rats: the role of endothelial nitric oxide synthase.
1. The aim of the present study was to determine whether ligustrazine (2,3,5,6-tetramethylpyrazine; TMP) exerts a cardioprotective effect during myocardial ischaemia reperfusion (IR), and to investigate the underlying mechanisms and the role of endothelial nitric oxide synthase (eNOS) in cardioprotection. 2. Sprague-Dawley rats were divided into a sham group and five IR groups: IR control, TMP pretreated, TMP + wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor), N(G) -nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) and TMP + L-NAME. ⋯ Wortmannin abrogated the phosphorylation of Akt and eNOS induced by TMP. 4. These data suggest that ligustrazine has anti-apoptotic and cardioprotective effects against myocardial IR injury and that it acts through the PI3K/Akt pathway. In addition, the phosphorylation of eNOS with subsequent NO production was found to be an important downstream effector that contributes significantly to the cardioprotective effect of TMP.
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Clin. Exp. Pharmacol. Physiol. · Nov 2011
Dalteparin dose-dependently increases ROTEM(®) thrombelastography parameters only at supratherapeutic anti-factor Xa levels: an in vitro study.
1. The low molecular weight heparin (LMWH) dalteparin is used, for example, to prevent primary venous thromboembolism in patients undergoing surgery or in medically ill patients. The anticoagulant activity of dalteparin can be monitored by measuring anti-factor Xa levels and activated partial thromboplastin time (aPTT); however, aPTT is an unreliable parameter in this case. ⋯ Moreover, the mean CFT value (EXTEM) increased from 97.7 ± 21.5 s at baseline to 187.6 ± 115.2 s (P = 0.0001) at a drug concentration of 10 μg/mL, which is greater than the therapeutic anti-factor Xa concentrations for LMWH. The results obtained when INTEM was used as the reagent were similar to those obtained using EXTEM. 4. In conclusion, the results indicate that the thrombelastograph ROTEM(®) can detect the anticoagulant effects of dalteparin only at supratherapeutic levels of anti-factor Xa.
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Clin. Exp. Pharmacol. Physiol. · Nov 2011
Presynaptic muscarinic and adenosine receptors are involved in 2 Hz-induced train-of-four fade caused by antinicotinic neuromuscular relaxants in the rat.
1. Train-of-four fade (TOF(fade) ) is a clinically useful parameter to monitor the degree of block of neuromuscular transmission in curarized patients. Experimentally, TOF(fade) has been attributed to the blockade of facilitatory nicotinic receptors on motor nerve terminals. ⋯ Blockade of the A(2A) receptor with 10 nmol/L ZM241385 partially reversed the TOF(fade) induced by d-tubocurarine, vecuronium and rocuronium, but not that caused by the 'pure' neuronal nicotinic receptor antagonist hexamethonium, unless one increased the concentration of ZM241385 to 50 nmol/L. 4. The data indicate that presynaptic M(1) , M(2) , A(1) and A(2A) receptors play a role in neuromuscular TOF(fade) caused by antinicotinic neuromuscular relaxants. Such interplay depends on adenosine tonus and on the affinity of neuromuscular blocking agents for neuronal versus muscular nicotinic receptors.