European journal of pharmacology
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The use of clonidine as a primary and adjuvant analgesic is well-documented. It is known that imidazoline and α2-adrenoceptors are involved in clonidine antinociception. Clonidine also produces antihypertensive actions mediated through the central nervous system. ⋯ Centhaquin citrate produced significant antinociception in mice (P<0.05) which was unaffected by JP-1302 (P>0.05) but blocked by BRL-44408 (tail-flick test: 49.75% decrease, P<0.05; hot-plate test: 49.12% decrease, P<0.05) and imiloxan (tail-flick test: 46.98% decrease, P<0.05; hot-plate test: 46.42% decrease, P<0.05). This is the first report demonstrating centhaquin citrate antinociception and its blockade by BRL-44408 and imiloxan. We conclude that α2A and α2B but not α2C adrenoceptors are involved in centhaquin antinociception in mice.
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The extracts or constituents from Corydalis impatiens are known to have many pharmacological activities. Tetrahydrocoptisine (THC), a protoberberine compound from Corydalis impatiens, was found to possess a potent anti-inflammatory effect in different acute or chronic inflammation model animals. Pretreatment with THC (i.p.) inhibited the paw and ear edema in the carrageenan-induced paw edema assay and xylene-induced ear edema assay, respectively. ⋯ THC inhibited the production of TNF-α and IL-6 by down-regulating LPS-induced IL-6 and TNF-α mRNA expression. Furthermore, it attenuated the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) as well as the expression of nuclear factor kappa B(NF-κB), in a concentration-dependent manner. Taken together, our data suggest that THC is an active anti-inflammatory constituent by inhibition of TNF-α, IL-6 and NO production possibly via down-regulation of NF-κB activation, phospho-ERK1/2 and phospho-p38MAPK signal pathways.
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The neuroprotective effect of DBZIM, a novel imidazolium compound, has previously been documented to slow down neurodegeneration in a mouse model of Parkinson's disease. In this study, we conducted behavioural studies and further investigated the neuroprotection in a rat Parkinsonian model induced by 6-hydroxydopamine (6-OHDA). DBZIM was found to significantly reduce the 6-OHDA-induced asymmetrical rotation and preferential usage of contralateral forelimbs. ⋯ In addition, DBZIM attenuated the activation of astrocytes and microglia. This suggests that anti-inflammation may be an additional mechanism underlying the DBZIM-mediated neuroprotection. These findings warrant further investigation of DBZIM as a promising and potent agent for the future treatment of Parkinson's disease.
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Ergotamine has been used in clinical practice for the acute treatment of migraine for over 90 years. So far, it is known that ergotamine interacts with diverse receptors (including α1/2-adrenoceptors, 5-HT1, 5-HT2 and D2-like receptors) and that produces increases in mean blood pressure which are significantly blocked by yohimbine, a classical α2-adrenoceptor antagonist with a moderate affinity for α1-adrenoceptors. Since α1/2-adrenoceptors mediate vasopressor and vasoconstrictor responses in the cardiovascular system, this study was designed to identify the α-adrenoceptor subtypes (α1A, α1B, α1D, α2A, α2B and α2C) involved in ergotamine-induced vasopressor responses in pithed rats. ⋯ Then, the vasopressor responses to intravenous (i.v.) bolus injections of ergotamine were determined after administration of vehicle or several α1⧸2-adrenoceptor antagonists. I.v. administration of the antagonists prazosin (α1, 0.1-30 µg/kg), rauwolscine (α2, 0.3-300 µg/kg), prazosin (0.1 µg/kg) plus rauwolscine (0.3 µg/kg), 5-methylurapidil (α1A, 100 and 300 µg/kg), L-765,314 (α1B, 100 and 300 µg/kg), BMY 7378 (α1D, 100 and 300 µg/kg), BRL44408 (α2A, 300 and 1000 µg/kg) and JP-1302 (α2C, 300 µg/kg), significantly blocked the vasopressor responses to ergotamine, whereas imiloxan (α2B, 1000 and 3000 µg/kg), JP-1302 (100 µg/kg) or the corresponding vehicles (saline 0.9%, propylene glycol 20% or dimethyl sulfoxide 10%; 1ml/kg) failed to modify the responses to ergotamine. The above results suggest that the vasopressor responses to ergotamine in pithed rats are mainly mediated by α1A-, α1B-, α1D-, α2A- and α2C-adrenoceptors and may explain its adverse/therapeutic effects.
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Valproate is widely used for migraine treatments, although precise mechanisms of its anticephalgic action are poorly understood. Migraine attacks are thought to occur due to trigemino-vascular system activation, which in turn, stimulates nociceptive transmission in trigemino-thalamo-cortical pathway. The ventroposteromedial (VPM) nucleus of the thalamus is considered to play a prominent role in neurobiology of headaches by serving as the highest subcortical relay for conveying nociceptive information from intra- and extra-cranial structures to the cortex. ⋯ Intravenous administration of valproate produced the dose-dependent suppression of both the ongoing activity of the thalamic VPM neurons and their responses to electrical stimulation of the dura mater. This effect was fast-developing (within 5 min) and short-lasting (no longer than 30 min). These data suggest that intravenous administration of valproate could produce a reduction of the thalamo-cortical nociceptive transmission associated with trigemino-vascular activation.