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https://www.readbyqxmd.com/read/28334978/therapeutic-window-of-dopamine-d2-3-receptor-occupancy-to-treat-psychosis-in-alzheimer-s-disease
#1
Suzanne Reeves, Emma McLachlan, Julie Bertrand, Fabrizia D Antonio, Stuart Brownings, Akshay Nair, Suki Greaves, Alan Smith, David Taylor, Joel Dunn, Paul Marsden, Robert Kessler, Robert Howard
Antipsychotic drugs, originally developed to treat schizophrenia, are used to treat psychosis, agitation and aggression in Alzheimer's disease. In the absence of dopamine D2/3 receptor occupancy data to inform antipsychotic prescribing for psychosis in Alzheimer's disease, the mechanisms underpinning antipsychotic efficacy and side effects are poorly understood. This study used a population approach to investigate the relationship between amisulpride blood concentration and central D2/3 occupancy in older people with Alzheimer's disease by combining: (i) pharmacokinetic data (280 venous samples) from a phase I single (50 mg) dose study in healthy older people (n = 20, 65-79 years); (ii) pharmacokinetic, 18F-fallypride D2/3 receptor imaging and clinical outcome data on patients with Alzheimer's disease who were prescribed amisulpride (25-75 mg daily) to treat psychosis as part of an open study (n = 28; 69-92 years; 41 blood samples, five pretreatment scans, 19 post-treatment scans); and (iii) 18F-fallypride imaging of an antipsychotic free Alzheimer's disease control group (n = 10, 78-92 years), to provide additional pretreatment data...
February 4, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334444/the-partial-dopamine-d2-receptor-agonist-aripiprazole-is-associated-with-weight-gain-in-adolescent-anorexia-nervosa
#2
Guido K W Frank, Megan E Shott, Jennifer O Hagman, Marissa A Schiel, Marisa C DeGuzman, Brogan Rossi
OBJECTIVE: Finding medication to support treatment of anorexia nervosa has been difficult. Neuroscience-based approaches may help in this effort. Recent brain imaging studies in adults and adolescents with anorexia nervosa suggest that dopamine-related reward circuits are hypersensitive and could provide a treatment target. METHODS: Here, we present a retrospective chart review of 106 adolescents with anorexia nervosa some of whom were treated with the dopamine D2 receptor partial agonist aripiprazole during treatment in a specialized eating disorder program...
March 23, 2017: International Journal of Eating Disorders
https://www.readbyqxmd.com/read/28331332/clinical-role-of-brexpiprazole-in-depression-and-schizophrenia
#3
REVIEW
Nishant B Parikh, Diana M Robinson, Anita H Clayton
Brexpiprazole, a serotonin-dopamine activity modulator, is the second D2 partial agonist to come to market and has been approved for the treatment of schizophrenia and as an adjunctive treatment in major depressive disorder. With less intrinsic activity than aripiprazole at the D2 receptor and higher potency at 5-HT2A, 5-HT1A, and α1B receptors, the pharmacological properties of brexpiprazole suggest a more tolerable side effect profile with regard to akathisia, extrapyramidal dysfunction, and sedation. While no head-to-head data are currently available, double-blind placebo-controlled studies show favorable results, with the number needed to treat (NNT) vs placebo of 6-15 for response in acute schizophrenia treatment and 4 for maintenance...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28327597/molecular-signaling-underlying-bulleyaconitine-a-baa-induced-microglial-expression-of-prodynorphin
#4
Teng-Fei Li, Hai-Yun Wu, Yi-Rui Wang, Xin-Yan Li, Yong-Xiang Wang
Bulleyaconitine (BAA) has been shown to possess antinociceptive activities by stimulation of dynorphin A release from spinal microglia. This study investigated its underlying signal transduction mechanisms. The data showed that (1) BAA treatment induced phosphorylation of CREB (rather than NF-κB) and prodynorphin expression in cultured primary microglia, and antiallodynia in neuropathy, which were totally inhibited by the CREB inhibitor KG-501; (2) BAA upregulated phosphorylation of p38 (but not ERK or JNK), and the p38 inhibitor SB203580 (but not ERK or JNK inhibitor) and p38β gene silencer siRNA/p38β (but not siRNA/p38α) completely blocked BAA-induced p38 phosphorylation and/or prodynorphin expression, and antiallodynia; (3) BAA stimulated cAMP production and PKA phosphorylation, and the adenylate cyclase inhibitor DDA and PKA inhibitor H-89 entirely antagonized BAA-induced prodynorphin expression and antiallodynia; (4) The Gs-protein inhibitor NF449 completely inhibited BAA-increased cAMP level, prodynorphin expression and antiallodynia, whereas the antagonists of noradrenergic, corticotrophin-releasing factor, A1 adenosine, formyl peptide, D1/D2 dopamine, and glucagon like-peptide-1 receptors failed to block BAA-induced antiallodynia...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326743/dopamine-receptors-modulate-t-lymphocytes-via-inhibition-of-camp-creb-signaling-pathway
#5
(no author information available yet)
OBJECTIVES: We have previously reported that dopamine D2-like receptors including D2, D3 and D4 receptors are more important in mediating modulation of T cells than dopamine D1-like receptors (D1 and D5 receptors). Here we aimed to clarify the role of D2-like receptors in regulation of differentiation and function of T lymphocyte subsets, including helper T (Th)1, Th2, Th17 and regulatory T (Treg) cells. METHODS: Lymphocytes, separated from the mesenteric lymph nodes of mice, were stimulated with concanavalin A (Con A) and treated with the D2-like receptor agonist quinpirole or the antagonist haloperidol...
December 22, 2016: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28324006/effects-of-season-and-estradiol-on-kndy-neuron-peptides-colocalization-with-d2-dopamine-receptors-and-dopaminergic-inputs-in-the-ewe
#6
Peyton Weems, Jeremy Smith, Iain J Clarke, Lique M Coolen, Robert L Goodman, Michael N Lehman
Seasonal reproduction in sheep is primarily due to a dramatic increase in the ability of estradiol (E2) to inhibit the pulsatile secretion of gonadotropin-releasing hormone (GnRH) during the non-breeding season (anestrus). Recent findings suggest that KNDy (kisspeptin/neurokinin B/dynorphin) neurons of the arcuate nucleus (ARC) play a key role in conveying this negative feedback influence, with dopaminergic projections from the retrochiasmatic area acting upon KNDy cells to decrease kisspeptin release and thus inhibit GnRH pulses...
January 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323555/influence-of-dopamine-related-genes-on-neurobehavioral-recovery-after-traumatic-brain-injury-during-early-childhood
#7
Amery Treble-Barna, Shari L Wade, Lisa J Martin, Valentina Pilipenko, Keith Owen Yeates, H Gerry Taylor, Brad G Kurowski
The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3...
March 21, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28322171/dopaminergic-modulation-of-sleep-wake-states
#8
Andrea Herrera-Solís, Wendy Herrera-Morales, Luis Núñez-Jaramillo, Oscar Arias-Carrión
The role of dopamine in sleep-wake regulation is associated as a wakefulness-promoting agent. For the clinical treatment of excessive daytime sleepiness, drugs have been commonly used to increase dopamine release. However, sleep disorders or lack of sleep is related to several dopamine-related disorders. The effects of dopaminergic agents, nevertheless, are mediated by two families of dopamine receptors, D1 and D2-like receptors; the first family increases adenylyl cyclase activity and the second inhibits adenylyl cyclase...
March 20, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28319198/methamphetamine-induces-shati-nat8l-expression-in-the-mouse-nucleus-accumbens-via-creb-and-dopamine-d1-receptor-dependent-mechanism
#9
Kyosuke Uno, Toh Miyazaki, Kengo Sodeyama, Yoshiaki Miyamoto, Atsumi Nitta
Shati/Nat8L significantly increased in the nucleus accumbens (NAc) of mice after repeated methamphetamine (METH) treatment. We reported that Shati/Nat8L overexpression in mouse NAc attenuated METH-induced hyperlocomotion, locomotor sensitization, and conditioned place preference. We recently found that Shati/Nat8L overexpression in NAc regulates the dopaminergic neuronal system via the activation of group II mGluRs by elevated N-acetylaspartylglutamate following N-acetylaspartate increase due to the overexpression...
2017: PloS One
https://www.readbyqxmd.com/read/28316587/characterization-of-the-antinociceptive-mechanisms-of-khat-extract-catha-edulis-in-mice
#10
Elham A Afify, Huda M Alkreathy, Ahmed S Ali, Hassan A Alfaifi, Lateef M Khan
This study investigated the antinociceptive mechanisms of khat extract (100, 200, and 400 mg/kg, i.p.) in four pain models: two thermic (hot plate, tail-flick) and two chemical (acetic acid, formalin) models. Male mice were pretreated intraperitoneally (i.p.) with the opioid receptor blocker naloxone (5 mg/kg), the cholinergic antagonist atropine (2 mg/kg), the selective α1 blocker prazosin (1 mg/kg), the dopamine D2 antagonist haloperidol (1.5 mg/kg), or the GABAA receptor antagonist, bicuculline (1 mg/kg) 15 minutes prior to i...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28314910/the-relationship-between-the-dopaminergic-system-and-depressive-symptoms-in-cervical-dystonia
#11
E Zoons, M A J Tijssen, Y E M Dreissen, J D Speelman, M Smit, J Booij
PURPOSE: Cervical dystonia (CD) is associated with tremor/jerks (50%) and psychiatric complaints (17-70%). The dopaminergic system has been implicated in the pathophysiology of CD in animal and imaging studies. Dopamine may be related to the motor as well as non-motor symptoms of CD. CD is associated with reduced striatal dopamine D2/3 (D2/3) receptor and increased dopamine transporter (DAT) binding. There are differences in the dopamine system between CD patients with and without jerks/tremor and psychiatric symptoms...
March 17, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28314679/an-analysis-of-the-rewarding-and-aversive-associative-properties-of-nicotine-in-the-neonatal-quinpirole-model-effects-on-glial-cell-line-derived-neurotrophic-factor-gdnf
#12
Russell W Brown, Seth L Kirby, Adam R Denton, John M Dose, Elizabeth D Cummins, Wesley Drew Gill, Katherine C Burgess
This study analyzed the associative properties of nicotine in a conditioned place preference (CPP) paradigm in adolescent rats neonatally treated with quinpirole (NQ) or saline (NS). NQ produces dopamine D2 receptor supersensitivity that persists throughout the animal's lifetime, and therefore has relevance towards schizophrenia. In two experiments, rats were ip administered quinpirole (1mg/kg) or saline from postnatal day (P)1-21. After an initial preference test at P42-43, animals were conditioned for eight consecutive days with saline or nicotine (0...
March 14, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28304244/intravitreally-administered-dopamine-d2-like-and-d4-but-not-d1-like-receptor-agonists-reduce-form-deprivation-myopia-in-tree-shrews
#13
Alexander H Ward, John T Siegwart, Michael R Frost, Thomas T Norton
We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5 µL intravitreal injections in the FD eye. The reference group received 0...
January 2017: Visual Neuroscience
https://www.readbyqxmd.com/read/28300398/novel-bivalent-ligands-based-on-the-sumanirole-pharmacophore-reveal-dopamine-d2-receptor-d2r-biased-agonism
#14
Alessandro Bonifazi, Hideaki Yano, Michael P Ellenberger, Ludovic Muller, Vivek Kumar, Mu-Fa Zou, Ning Sheng Cai, Adrian M Guerrero, Amina S Woods, Lei Shi, Amy Hauck Newman
The development of bivalent ligands has attracted interest as a way to potentially improve the selectivity and/or affinity for a specific receptor subtype. The ability to bind two distinct receptor binding sites simultaneously can allow the selective activation of specific G-protein dependent or β-arrestin-mediated cascade pathways. Herein, we developed an extended SAR study using sumanirole (1) as the primary pharmacophore. We found that substitutions in the N-1- and/or N-5-positions, physiochemical properties of those substituents, and secondary aromatic pharmacophores can enhance agonist efficacy for the cAMP inhibition mediated by Gi/o-proteins, while reducing or suppressing potency and efficacy toward β-arrestin recruitment...
March 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28297025/association-of-stimulant-use-with-dopaminergic-alterations-in-users-of-cocaine-amphetamine-or-methamphetamine-a-systematic-review-and-meta-analysis
#15
Abhishekh H Ashok, Yuya Mizuno, Nora D Volkow, Oliver D Howes
Importance: Stimulant use disorder is common, affecting between 0.3% and 1.1% of the population, and costs more than $85 billion per year globally. There are no licensed treatments to date. Several lines of evidence implicate the dopamine system in the pathogenesis of substance use disorder. Therefore, understanding the nature of dopamine dysfunction seen in stimulant users has the potential to aid the development of new therapeutics. Objective: To comprehensively review the in vivo imaging evidence for dopaminergic alterations in stimulant (cocaine, amphetamine, or methamphetamine) abuse or dependence...
March 15, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28294132/5-ht2c-agonists-modulate-schizophrenia-like-behaviors-in-mice
#16
Vladimir M Pogorelov, Ramona M Rodriguiz, Jianjun Cheng, Mei Huang, Claire M Schmerberg, Herbert Y Meltzer, Bryan L Roth, Alan P Kozikowski, William C Wetsel
All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side-effects, and provide only partial amelioration of negative and cognitive symptoms. The heterogeneity of pharmacological responses in schizophrenic patients suggests additional drug-targets may be effective in improving aspects of this syndrome. Recent evidence suggests that 5-HT2C receptors may be a promising target for schizophrenia since their activation reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action), they are expressed almost exclusively in CNS, and have weight-loss promoting capabilities...
March 15, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28291301/-acute-dystonia-due-to-aripiprazole-use-in-two-children-with-autism-spectrum-disorder-in-the-first-five-years-of-life
#17
Mustafa Küçükköse, Bürge Kabukçu Başay
Autism spectrum disorders (ASD) are neuropsychiatric disorders characterized by impairment in social interactions, in verbal and non-verbal communication, and restricted and stereotyped patterns of interest and behavior within the first 3 years of life. Pharmacologic interventions may be needed for the treatment of temper tantrums, aggression, hyperactivity, and stereotypes in children with ASD. The approval of aripiprazole by the United States Food and Drug Administration (USFDA) for the treatment of temper tantrums in children and adolescents with ASD has gained increased interest for the use in these patients...
2017: Türk Psikiyatri Dergisi, Turkish Journal of Psychiatry
https://www.readbyqxmd.com/read/28289283/the-dopamine-hypothesis-of-bipolar-affective-disorder-the-state-of-the-art-and-implications-for-treatment
#18
REVIEW
A H Ashok, T R Marques, S Jauhar, M M Nour, G M Goodwin, A H Young, O D Howes
Bipolar affective disorder is a common neuropsychiatric disorder. Although its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades. The increased use of antidopaminergics in the treatment of this disorder and new in vivo neuroimaging and post-mortem studies makes it timely to review this theory. To do this, we conducted a systematic search for post-mortem, pharmacological, functional magnetic resonance and molecular imaging studies of dopamine function in bipolar disorder...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28284952/importance-of-d1-and-d2-receptor-stimulation-for-the-induction-and-expression-of-cocaine-induced-behavioral-sensitization-in-preweanling-rats
#19
Sanders A McDougall, Krista N Rudberg, Ana Veliz, Janhavi M Dhargalkar, Aleesha S Garcia, Loveth C Romero, Ashley E Gonzalez, Alena Mohd-Yusof, Cynthia A Crawford
The behavioral manifestations of psychostimulant-induced sensitization vary markedly between young and adult rats, suggesting that the neural mechanisms mediating this phenomenon differ across ontogeny. In this project we examined the importance of D1 and D2 receptors for the induction and expression of cocaine-induced behavioral sensitization during the preweanling period. In the behavioral experiments, rats were injected with reversible D1 and/or D2 antagonists (SCH23390 and/or raclopride) or an irreversible receptor antagonist (EEDQ) either before cocaine administration on the pretreatment day (induction) or before cocaine challenge on the test day (expression)...
March 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28283756/dopamine-t-cells-and-multiple-sclerosis-ms
#20
REVIEW
Mia Levite, Franca Marino, Marco Cosentino
Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others...
March 10, 2017: Journal of Neural Transmission
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