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Involvement of descending pain control system regulated by orexin receptor signaling in the induction of central post-stroke pain in mice.
In this study, we tested the role of orexin-A in CPSP induction in mice. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). CPSP was assessed by von Frey test. Colocalization of orexin 1 receptor (OX1R) with various neuron markers were determined by double-immunofluorescence. The hindpaw withdrawal responses to mechanical stimuli were significantly increased 3 days post-BCAO compared with those of sham groups. ICV injection of orexin-A dose-dependently suppressed BCAO-induced mechanical allodynia. These effects were inhibited by pre-treatment with SB334867 (an OX1R antagonist; ICV inject...
Source: European Journal of Pharmacology - February 17, 2020 Category: Drugs & Pharmacology Authors: Matsuura W, Nakamoto K, Tokuyama S Tags: Eur J Pharmacol Source Type: research

Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron
In this study, we evaluated whether nicotine could suppress BCAO-induced mechanical allodynia through the activation of orexinergic neurons. Mice were subjected to BCAO for 30 min. Mechanical hypersensitivity was assessed by the von Frey test. BCAO mice showed hypersensitivity to mechanical stimuli three days after BCAO surgery. The intracerebroventricular injection of nicotine suppressed BCAO-induced mechanical hypersensitivity in a dose-dependent manner. These effects were inhibited by α7 or α4β2-nicotinic receptor antagonists. After nicotine injection, the level of c-fos, a neuronal activity marker, increased in the ...
Source: European Journal of Pharmacology - January 27, 2023 Category: Drugs & Pharmacology Authors: Kazuo Nakamoto Wataru Matsuura Shogo Tokuyama Source Type: research

The metabotropic glutamate 2/3 receptor agonist LY379268 induces anxiety-like behavior at the highest dose tested in two rat models of anxiety.
Abstract The activation of Group II metabotropic glutamate 2/3 (mGlu2/3) receptors reduces the excessive glutamate release that is hypothesized to be associated with neurodegenerative and psychiatric disorders. LY379268 is a highly potent mGlu2/3 receptor agonist that has shown efficacy in several animal models of stroke, epilepsy, drug abuse, schizophrenia, and pain. The present study investigated the effects of LY379268 on anxiety-like behavior in rats assessed in the light/dark and open field tests. The effects of LY379268 on motility in a locomotor activity chamber were also investigated in rats. Administratio...
Source: European Journal of Pharmacology - June 11, 2013 Category: Drugs & Pharmacology Authors: Grivas V, Markou A, Pitsikas N Tags: Eur J Pharmacol Source Type: research

Roles of subunit phosphorylation in regulating glutamate receptor function.
Abstract Protein phosphorylation is an important mechanism for regulating ionotropic glutamate receptors (iGluRs). Early studies have established that major iGluR subtypes, including α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and N-methyl-D-aspartate (NMDA) receptors, are subject to phosphorylation. Multiple serine, threonine, and tyrosine residues predominantly within the C-terminal regions of AMPA receptor and NMDA receptor subunits have been identified as sensitive phosphorylation sites. These distinct sites undergo either constitutive phosphorylation or activity-dependent phosphoryl...
Source: European Journal of Pharmacology - November 28, 2013 Category: Drugs & Pharmacology Authors: Wang JQ, Guo ML, Jin DZ, Xue B, Fibuch EE, Mao LM Tags: Eur J Pharmacol Source Type: research

N-3 polyunsaturated fatty acids in animal models with neuroinflammation: An update.
Abstract Neuroinflammation is a characteristic of a multitude of neurological and psychiatric disorders. Modulating inflammatory pathways offers a potential therapeutic target in these disorders. Omega-3 polyunsaturated fatty acids have anti-inflammatory and pro-resolving properties in the periphery, however, their effect on neuroinflammation is less studied. This review summarizes 61 animal studies that tested the effect of omega-3 polyunsaturated fatty acids on neuroinflammatory outcomes in vivo in various models including stroke, spinal cord injury, aging, Alzheimer's disease, Parkinson's disease, lipopolysacch...
Source: European Journal of Pharmacology - May 30, 2015 Category: Drugs & Pharmacology Authors: Trépanier MO, Hopperton KE, Orr SK, Bazinet RP Tags: Eur J Pharmacol Source Type: research

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?
Abstract Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis. Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of...
Source: European Journal of Pharmacology - February 4, 2016 Category: Drugs & Pharmacology Authors: Javid FA, Phillips RM, Afshinjavid S, Verde R, Ligresti A Tags: Eur J Pharmacol Source Type: research

Pharmacological potential of JWH133, a cannabinoid type 2 receptor agonist in neurodegenerative, neurodevelopmental and neuropsychiatric diseases
Eur J Pharmacol. 2021 Jul 29:174398. doi: 10.1016/j.ejphar.2021.174398. Online ahead of print.ABSTRACTThe pharmacological activation of cannabinoid type 2 receptors (CB2R) gained attention due to its ability to mitigate neuroinflammatory events without eliciting psychotropic activities, a limiting factor for the drugs targeting cannabinoid type 1 receptors (CB1R). Therefore, ligands activating CB2R are receiving enormous importance for therapeutic targeting in numerous diseases including neurodegenerative, neuropsychiatric and neurodevelopmental disorders as well as traumatic injuries and neuropathic pain where neuroinflam...
Source: European Journal of Pharmacology - August 1, 2021 Category: Drugs & Pharmacology Authors: Hebaallah Mamdouh Hashiesh Niraj Kumar Jha Charu Sharma Piyush Kumar Gupta Saurabh Kumar Jha Chandragouda R Patil Sameer N Goyal Shreesh K Ojha Source Type: research

Mechanisms of acid-sensing ion channels inhibition by nafamostat, sepimostat and diminazene
Eur J Pharmacol. 2022 Nov 17:175394. doi: 10.1016/j.ejphar.2022.175394. Online ahead of print.ABSTRACTAcid-sensing ion channels (ASICs) are blocked by many cationic compounds. Mechanisms of action, which may include pore block, modulation of activation and desensitization, need systematic analysis to allow predictable design of new potent and selective drugs. In this work, we studied the action of the serine protease inhibitors nafamostat, sepimostat, gabexate and camostat, on native ASICs in rat giant striatal interneurons and recombinant ASIC1a and ASIC2a channels, and compared it to that of well-known small molecule ASI...
Source: European Journal of Pharmacology - November 20, 2022 Category: Drugs & Pharmacology Authors: Arseniy S Zhigulin Denis B Tikhonov Oleg I Barygin Source Type: research