European journal of pharmacology
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The mechanism of the analgesic activity of paracetamol (acetaminophen), one of the most widely used drugs for the treatment of pain, is still not clear. Here we show that in rats, using the hot plate test, the analgesic effect of paracetamol is prevented by two antagonists at cannabinoid CB1 receptors (AM281 and SR141716A) at doses that prevent the analgesic activity of the cannabinoid CB1 agonist HU210. Our present results suggest that paracetamol-induced antinociception involves the cannabinoid system.
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Comparative Study
Comparison of effects of formoterol and BRL 37344 on isolated term-pregnant rat myometrial strips in vitro.
This study was designed to compare the effects of beta-adrenoceptor agonists formoterol and BRL 37344 on spontaneous contractions and the levels of cAMP and cGMP of myometrial strips isolated from timed-pregnant rats. Myometrial strips were obtained from term-pregnant Wistar albino rats (n=12), mounted in organ baths and tested for changes in isometric tension in response to formoterol and BRL 37344. We evaluated the effect of increasing concentrations of formoterol and BRL 37344 on oxytocin-induced myometrial contractions and on contractions of myometrial smooth muscle pretreated with metoprolol, ICI 118.551 and SR 59230A (beta1, beta2, beta3-adrenoceptor antagonist, respectively, 10(-6) M). ⋯ Formoterol and BRL 37344 increased cAMP levels. BRL 37344 increased cGMP levels in BRL 37344 group more than control group, but this increase is less significant than cAMP levels (P>0.05). Formoterol and BRL 37344 decreased amplitude of myometrial contractions with similar potency, but efficacy of formoterol was better than BRL 37344.
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Controlled Clinical Trial
Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine.
Evidence for an analgesic interaction between delta-9-tetrahydrocannabinol (Delta(9)-THC) and morphine was sought using an experimental pain model applied to normal volunteers. The study incorporated a double blinded, four treatment, four period, four sequence, crossover design. Subjects received Delta(9)-THC 5 mg orally or placebo and 90 min later morphine 0.02 mg/kg intravenously or placebo. ⋯ The surprisingly limited reported experimental experience in humans does not support a role for Delta(9)-THC as an analgesic or as an adjunct to cannabinoid analgesia, except for our finding of synergy limited to the affective component of pain. Comparison of our results with those of others suggests that extrapolation from experimental pain models to the clinic is not likely to be a straight-forward process. Future studies of Delta(9)-THC or other cannabinoids in combination with opiates should focus upon clinical rather than experimental pain.
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Comparative Study
Antiproliferative and antiangiogenic effects of 3-methylcholanthrene, an aryl-hydrocarbon receptor agonist, in human umbilical vascular endothelial cells.
There is increasing interest in the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and polycyclic aromatic hydrocarbons on cardiovascular diseases. Their chemical structures are similar, although polycyclic aromatic hydrocarbons contain no chlorine as does TCDD. The biochemical mechanism of their action is mainly mediated by the aryl hydrocarbon receptor. ⋯ We also demonstrated that cell adhesion signaling (phosphorylated focal adhesion kinase (FAK)) decreased upon 3-MC treatment, suggesting that cell adhesion inhibited by 3-MC might be due to inhibition of cell adhesion signaling. Additionally, alpha-naphthoflavon (alpha-NF) ameliorated the effects of 3-MC on cell permeability, adhesion and tube formation, indicating the involvement of the aryl hydrocarbon receptor in angiogenesis. The results suggest that the adverse effects of 3-MC are mainly mediated by the aryl hydrocarbon receptor and not via increased oxidative stress.
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HR-1 hairless mice fed with a special diet develop atopic-like dry skin, characterized by increased transepidermal water loss, and prolonged bouts of spontaneous scratching. In this study, the role of the skin barrier dysfunction in the prolongation of scratching was evaluated. Although the prolonged scratching was dose-dependently inhibited by opioid receptor antagonist naloxone, neither H(1) receptor antagonist, mepyramine, nor 5-HT(1/2) receptor antagonist, methysergide, affected it. ⋯ Due to this alleviation in barrier dysfunction, the prolongation of scratching was significantly suppressed. However, when the barrier dysfunction relapsed, the scratching worsened. Taken together, a skin barrier dysfunction is associated with the itch-related response.