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https://www.readbyqxmd.com/read/28935562/n-2-methoxyphenyl-benzenesulfonamide-a-novel-regulator-of-neuronal-g-protein-gated-inward-rectifier-k-channels
#1
Kenneth B Walsh, Elaine A Gay, Bruce E Blough, David W Geurkink
G protein-gated inward rectifier K(+) (GIRK) channels are members of the super-family of proteins known as inward rectifier K(+) (Kir) channels and are expressed throughout the peripheral and central nervous systems. Neuronal GIRK channels are the downstream targets of a number of neuromodulators including opioids, somatostatin, dopamine and cannabinoids. Previous studies have demonstrated that the ATP-sensitive K(+) channel, another member of the Kir channel family, is regulated by sulfonamide drugs. Therefore, to determine if sulfonamides also modulate GIRK channels, we screened a library of arylsulfonamide compounds using a GIRK channel fluorescent assay that utilized pituitary AtT20 cells expressing GIRK channels along with the somatostatin type-2 and -5 receptors...
September 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28933969/psychopharmacological-advances-in-eating-disorders
#2
Hubertus Himmerich, Janet Treasure
Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) are the primary eating disorders (EDs). The only psychopharmacological treatment options for EDs with approval in some countries include fluoxetine for BN and lisdexamfetamine for BED. Given the high comorbidity and genetic correlations with other psychiatric disorders, it seems possible that novel medications for these conditions might also be effective in EDs. Areas Covered: The current scientific literature has increased our understanding of how medication could be beneficial for patients with EDs on a molecular, functional and behavioral level...
September 21, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28925883/novel-therapeutics-in-glaucoma-management
#3
Claudio Bucolo, Chiara Bianca Maria Platania, Filippo Drago, Michele Reibaldi, Vincenza Bonfiglio, Teresio Avitabile, Maurizio Uva
Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell death and alterations of visual field. Elevated intraocular pressure (IOP) is considered the main risk factor of glaucoma, even though other factors cannot be ruled out, such as epigenetic mechanisms. An overview of the ultimate promising experimental drugs to manage glaucoma has been provided. In particular, we have focused on purinergic ligands, KATP channel activators, gases (nitric oxide, carbon monoxide and hydrogen sulfide), non-glucocorticoid steroidal compounds, neurotrophic factors, PI3K/Akt activators, citicoline, histone deacetylase inhibitors, cannabinoids, dopamine and serotonin receptors ligands, small interference RNA, and Rho kinase inhibitors...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28912087/endocannabinoid-mechanism-in-amphetamine-type-stimulant-use-disorders-a-short-review
#4
REVIEW
Hang Su, Min Zhao
Recent evidence shows that the endocannabinoid system is involved in amphetamine-type stimulants (ATS) use disorders. To elucidate the role of the endocannabinoid system in ATS addiction, we reviewed results of studies using cannabinoid receptor agonists, antagonists as well as knockout model. The endocannabinoid system seems to play a role in reinstatement and relapse of ATS addiction and ATS-induced psychiatric symptoms. The molecular mechanisms of this system remains unclear, the association with dopamine system in nucleus accumbens is most likely involved...
September 11, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28861502/cannabinoids-in-parkinson-s-disease
#5
REVIEW
Mario Stampanoni Bassi, Andrea Sancesario, Roberta Morace, Diego Centonze, Ennio Iezzi
The endocannabinoid system plays a regulatory role in a number of physiological processes and has been found altered in different pathological conditions, including movement disorders. The interactions between cannabinoids and dopamine in the basal ganglia are remarkably complex and involve both the modulation of other neurotransmitters (γ-aminobutyric acid, glutamate, opioids, peptides) and the activation of different receptors subtypes (cannabinoid receptor type 1 and 2). In the last years, experimental studies contributed to enrich this scenario reporting interactions between cannabinoids and other receptor systems (transient receptor potential vanilloid type 1 cation channel, adenosine receptors, 5-hydroxytryptamine receptors)...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/28861501/palmitoylethanolamide-modulates-gpr55-receptor-signaling-in-the-ventral-hippocampus-to-regulate-mesolimbic-dopamine-activity-social-interaction-and-memory-processing
#6
Cecilia Kramar, Michael Loureiro, Justine Renard, Steven R Laviolette
Introduction: The GPR55 receptor has been identified as an atypical cannabinoid receptor and is implicated in various physiological processes. However, its functional role in the central nervous system is not currently understood. The presence of GPR55 receptor in neural regions such as the ventral hippocampus (vHipp), which is critical for cognition, recognition memory, and affective processing, led us to hypothesize that intra-vHipp GPR55 transmission may modulate mesolimbic activity states and related behavioral phenomena...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/28826532/endocannabinoid-analytical-methodologies-techniques-that-drive-discoveries-that-drive-techniques
#7
Fabiana Piscitelli, Heather B Bradshaw
Identification of the two major endogenous cannabinoid ligands, known as endocannabinoids, N-arachidonoyl-ethanolamine (anandamide, AEA) and 2-arachidonoyl-glycerol (2-AG), opened the way for the identification and isolation of other lipid congeners, all derivatives of fatty acids and related to the Endocannabinoid System. The nomenclature of this anandamide-type class of lipids is evolving as new species are discovered all the time. However, they each fall under the larger umbrella of lipids that are a conjugation of a fatty acid with an amine through and amide bond, which we will refer to as lipoamines...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28766743/mouse-retinal-ganglion-cell-signalling-is-dynamically-modulated-through-parallel-anterograde-activation-of-cannabinoid-and-vanilloid-pathways
#8
Andrew O Jo, Jennifer M Noel, Monika Lakk, Oleg Yarishkin, Daniel A Ryskamp, Koji Shibasaki, Maureen A McCall, David Križaj
How retinal ganglion cells (RGCs) process and integrate synaptic, mechanical, swelling stimuli with light inputs is an area of intense debate. The nociceptive cation channel TRPV1 (transient receptor potential vanilloid type 1) modulates RGC Ca(2+) signals and excitability yet the proportion of RGCs that express it remains unclear. Further, TRPV1's response to endocannabinoids (eCBs), the putative endogenous retinal activators unknown, as is the potential modulation by cannabinoid receptors (CBRs). The expression of TRPV1 in RGCs from the Ai9:Trpv1 reporter mouse was nonuniform with peak density in the early- and mid-peripheral retina...
August 2, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28734930/bidirectional-allosteric-interactions-between-cannabinoid-receptor-1-cb1-and-dopamine-receptor-2-long-d2l-heterotetramers
#9
Amina M Bagher, Robert B Laprairie, J Thomas Toguri, Melanie E M Kelly, Eileen M Denovan-Wright
Type 1 cannabinoid (CB1) and dopamine 2 long form (D2L) receptors can physically interact to form heteromers that display unique pharmacology in vitro compared to homomeric complexes. Co-expression of CB1 and D2L and co-application of CB1 and D2 agonists increases cAMP levels while administration of either agonist alone decreases cAMP levels. To understand the observed co-agonist response, our first goal of the current study was to define the stoichiometry of CB1/D2L/Gα protein complexes. Using bioluminescence resonance energy transfer 2 (BRET(2)), we confirmed that, CB1 homodimers, D2L homodimers, and CB1/D2L heteromers are formed...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28734904/identifying-novel-members-of-the-wntless-interactome-through-genetic-and-candidate-gene-approaches
#10
Jessica Petko, Trevor Tranchina, Goral Patel, Robert Levenson, Stephanie Justice-Bitner
Wnt signaling is an important pathway that regulates several aspects of embryogenesis, stem cell maintenance, and neural connectivity. We have recently determined that opioids decrease Wnt secretion, presumably by inhibiting the recycling of the Wnt trafficking protein Wntless (Wls). This effect appears to be mediated by protein-protein interaction between Wls and the mu-opioid receptor (MOR), the primary cellular target of opioid drugs. The goal of this study was to identify novel protein interactors of Wls that are expressed in the brain and may also play a role in reward or addiction...
July 20, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28733540/am1241-alleviates-mptp-induced-parkinson-s-disease-and-promotes-the-regeneration-of-da-neurons-in-pd-mice
#11
Jun Shi, Qiong Cai, Jingxing Zhang, Xiaolie He, Yigang Liu, Rongrong Zhu, Lingjing Jin
The main pathological feature of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra. In this study, we investigated the role of cannabinoid receptor 2 (CB2R) agonist AM1241 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a mouse model of PD. Upon treatment with AM1241, the decreased CB2R level in the PD mouse brain was reversed and the behavior score markedly elevated, accompanied with a dose-dependent increase of dopamine and serotonin. In addition, western blot assay and immunostaining results suggested that AM1241 significantly activated PI3K/Akt/MEK phosphorylation and increased the expression of Parkin and PINK1, both in the substantia nigra and hippocampus...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28728428/consequence-of-dopamine-d2-receptor-blockade-on-the-hyperphagic-effect-induced-by-cannabinoid-cb1-and-cb2-receptors-in-layers
#12
M Khodadadi, M Zendehdel, A Baghbanzadeh, V Babapour
1. Endocannabinoids (ECBs) and their receptors play a regulatory function on several physiological processes such as feed-intake behaviour, mainly in the brain. This study was carried out in order to investigate the effects of the dopaminergic D1 and D2 receptors on CB1/CB2 ECB receptor-induced hyperphagia in 3-h feed-deprived neonatal layer chickens. 2. A total of 8 experiments were designed to explore the interplay of these two modulatory systems on feed intake in neonatal chickens. In Experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, l-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), 2-AG (2-arachidonoylglycerol as CB1 receptor agonist; 2 µg) and co-administration of l-DOPA (125 nmol) plus 2-AG (2 µg)...
August 16, 2017: British Poultry Science
https://www.readbyqxmd.com/read/28701511/n-arachidonoyl-dopamine-modulates-acute-systemic-inflammation-via-nonhematopoietic-trpv1
#13
Samira K Lawton, Fengyun Xu, Alphonso Tran, Erika Wong, Arun Prakash, Mark Schumacher, Judith Hellman, Kevin Wilhelmsen
N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28669034/cannabinoid-reward-and-aversion-effects-in-the-posterior-ventral-tegmental-area-are-mediated-through-dissociable-opiate-receptor-subtypes-and-separate-amygdalar-and-accumbal-dopamine-receptor-substrates
#14
Tasha Ahmad, Steven R Laviolette
RATIONALE: The ventral tegmental area (VTA) and its projections to the basolateral amygdala (BLA) and nucleus accumbens (NAc) are critical for cannabinoid-related motivational effects. Cannabinoid CB1 receptor (CB1R) transmission modulates VTA dopamine (DA) neuron activity and previous reports demonstrate anatomically segregated effects of CB1R transmission in the VTA. However, the underlying pharmacological and anatomical regions responsible for these effects are currently unknown. OBJECTIVES: The objective of the study is to characterize the motivational effects of localized anterior vs...
August 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28660730/fatty-acid-amide-hydrolase-faah-inactivation-confers-enhanced-sensitivity-to-nicotine-induced-dopamine-release-in-the-mouse-nucleus-accumbens
#15
Francisco J Pavon, Antonia Serrano, Nimish Sidhpura, Ilham Polis, David Stouffer, Fernando Rodriguez de Fonseca, Benjamin F Cravatt, Rémi Martin-Fardon, Loren H Parsons
Nicotine exerts its rewarding effects by promoting an increase in dopamine (DA) release in the nucleus accumbens (NAc), and this process is influenced by the endocannabinoid system. Fatty acid amide hydrolase (FAAH) is the main enzyme responsible for the degradation of the endocannabinoid anandamide and other non-cannabinoid N-acylethanolamines. Previous research has reported that both genetic deletion and pharmacological inhibition of FAAH enhance nicotine-induced conditioned place preference at low doses...
June 29, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28653666/endocannabinoid-regulation-of-reward-and-reinforcement-through-interaction-with-dopamine-and-endogenous-opioid-signaling
#16
J M Wenzel, J F Cheer
The endocannabinoid system (eCB) is implicated in the mediation of both reward and reinforcement. This is evidenced by the ability of exogenous cannabinoid drugs to produce hedonia and maintain self-administration in both human and animal subjects. eCBs similarly facilitate behaviors motivated by reward through interaction with the mesolimbic dopamine (DA) and endogenous opioid systems. Indeed, eCB signaling in the ventral tegmental area stimulates activation of midbrain DA cells and promotes DA release in terminal regions such as the nucleus accumbens (NAc)...
June 27, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28634109/cannabis-associated-psychosis-neural-substrate-and-clinical-impact
#17
REVIEW
R M Murray, A Englund, A Abi-Dargham, D A Lewis, M Di Forti, C Davies, M Sherif, P McGuire, D C D'Souza
Prospective epidemiological studies have consistently demonstrated that cannabis use is associated with an increased subsequent risk of both psychotic symptoms and schizophrenia-like psychoses. Early onset of use, daily use of high-potency cannabis, and synthetic cannabinoids carry the greatest risk. The risk-increasing effects are not explained by shared genetic predisposition between schizophrenia and cannabis use. Experimental studies in healthy humans show that cannabis and its active ingredient, delta-9-tetrahydrocannabinol (THC), can produce transient, dose-dependent, psychotic symptoms, as well as an array of psychosis-relevant behavioral, cognitive and psychophysiological effects; the psychotogenic effects can be ameliorated by cannabidiol (CBD)...
June 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28619471/oral-haloperidol-or-olanzapine-intake-produces-distinct-and-region-specific-increase-in-cannabinoid-receptor-levels-that-is-prevented-by-high-fat-diet
#18
Foteini Delis, Lauren Rosko, Aditya Shroff, Kenneth E Leonard, Panayotis K Thanos
Clinical studies show higher levels of cannabinoid CB1 receptors (CB1R) in the brain of schizophrenic patients while preclinical studies report a significant functional interaction between dopamine D2 receptors and CB1Rs as well as an upregulation of CB1Rs after antipsychotic treatment. These findings prompted us to study the effects of chronic oral intake of a first and a second generation antipsychotic, haloperidol and olanzapine, on the levels and distribution of CB1Rs in the rat brain. Rats consumed either regular chow or high-fat food and drank water, haloperidol drinking solution (1...
June 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28579186/endocannabinoid-modulation-of-homeostatic-and-non-homeostatic-feeding-circuits
#19
REVIEW
Benjamin K Lau, Daniela Cota, Luigia Cristino, Stephanie L Borgland
The endocannabinoid system has emerged as a key player in the control of eating. Endocannabinoids, including 2-arachidonoylglycerol (2-AG) and anandamide (AEA), modulate neuronal activity via cannabinoid 1 receptors (CB1Rs) in multiple nuclei of the hypothalamus to induce or inhibit food intake depending on nutritional and hormonal status, suggesting that endocannabinoids may act in the hypothalamus to integrate different types of signals informing about the animal's energy needs. In the mesocorticolimbic system, (endo)cannabinoids modulate synaptic transmission to promote dopamine release in response to palatable food...
June 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28577135/a-review-of-adjunctive-cns-medications-used-for-the-treatment-of-post-surgical-pain
#20
REVIEW
Ajit Rai, Howard Meng, Aliza Weinrib, Marina Englesakis, Dinesh Kumbhare, Liza Grosman-Rimon, Joel Katz, Hance Clarke
Inadequate post-operative pain management can have significant impacts on patients' quality of life. Effective management of acute pain after surgery is important for early mobilization and discharge from hospital, patient satisfaction, and overall well-being. Utilizing multimodal analgesic strategies has become the mainstay of acute post-operative pain management. A comprehensive search was performed, assessing the published or otherwise publically available literature on different central nervous system (CNS) drugs [excluding opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and acetaminophen] and their uses to treat acute post-surgical pain...
July 2017: CNS Drugs
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