European journal of pharmacology
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Sinomenine is an alkaloid originally isolated from the root of the plant Sinomenium acutum. It is used in traditional medicine in China to treat rheumatic arthritis. In the present study, we evaluated the potential antinociceptive effects of sinomenine in rodents with nociceptive, inflammatory and neuropathic pain. ⋯ Finally, sinomenine effectively alleviated mechanical and cold allodynia in rats and mice after injury to peripheral nerve or spinal cord. The analgesic effect of sinomenine is not associated with side effects and is not reversed by the opioid receptor antagonist naloxone. Our results showed that sinomenine has a wide spectrum analgesic effect in rodent models of nociceptive, inflammatory and neuropathic pain.
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Inhibitors of the metabolism of the endogenous cannabinoid ligand anandamide by fatty acid amide hydrolase (FAAH) reduce the gastric damage produced by non-steroidal anti-inflammatory agents and synergise with them in experimental pain models. This motivates the design of compounds with joint FAAH/cyclooxygenase (COX) inhibitory activity. Here we present data on the N-(3-methylpyridin-2-yl)amide derivatives of flurbiprofen and naproxen (Flu-AM1 and Nap-AM1, respectively) with respect to their properties towards these two enzymes. ⋯ Nap-AM1 was a less potent inhibitor of COX. Flu-AM1 at low micromolar concentrations inhibited the FAAH-driven uptake of [(3)H]anandamide into RBL2H3 basophilic leukaemia cells in vitro, but did not penetrate the brain in vivo sufficiently to block the binding of [(18)F]DOPP to brain FAAH. It is concluded that Flu-AM1 is a dual-action inhibitor of FAAH and COX that may be useful in exploring the optimal balance of effects on these two enzyme systems in producing peripheral alleviation of pain and inflammation in experimental models.
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Allergens can induce anaphylactic shock and death due to serve hypotension. Potassium channel blockers (K(+)(ATP)) such as glyburide (GLY) induce vasoconstriction. The effect of (K(+)(ATP)) channel blockers on anaphylactic shock is poorly understood. ⋯ PGE(2) increased in G3-SG; PGF(2) increased in G2-SC and G3-SG. Na(+) and Ca (++) concentration decreased in sensitized rats but reversed in treated groups, without change in K(+) concentration. In conclusion, our data suggest that administration of GLY reduced hypotension and increases survival time in rat anaphylactic shock.
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Allergens can induce anaphylactic shock and death due to severe hypotension. Potassium channel blockers (K(+)ATP) such as glyburide (GLY) induce vasoconstriction. The effect of K(+)ATP channel blockers on anaphylactic shock is poorly understood. ⋯ PGE2 increased in G3(-)SG; PGF2 increased in G2-SC and G3(-)SG. Na(+) and Ca(++) concentration decreased in sensitized rats but reversed in treated groups, without change in K(+) concentration. In conclusion, our data suggest that administration of GLY reduces hypotension and increases survival time in rat anaphylactic shock.
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α2-Adrenoceptors were first described as presynaptic receptors inhibiting the release of various transmitters from neurons in the central and peripheral nervous systems. In vitro studies have confirmed that α2A, α2B and α2C subtypes inhibited noradrenaline release from postganglionic sympathetic neurons but no study has been reported their involvement in the vasopressor sympathetic outflow in vivo. Thus, this study analysed the subtype(s) involved in the inhibition produced by the α2-adrenoceptor agonist, B-HT 933, on the vasopressor sympathetic outflow. ⋯ The sympatho-inhibition elicited by B-HT 933 was: (i) unaffected by vehicles (1 ml/kg); (ii) partially antagonised by BRL44408 (300 μg/kg; α2A), imiloxan (3000 μg/kg; α2B) and/or JP-1302 (300 μg/kg; α2C) given separately; and (iii) completely blocked by rauwolscine (300 μg/kg) or the combination of BRL44408 (300 μg/kg)+imiloxan (3000 μg/kg)+JP-1302 (300 μg/kg). The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. These results suggest that the vasopressor sympatho-inhibition to B-HT 933 is primarily mediated by activation of α2A/2B/2C-adrenoceptors in pithed rats.