Dopamine antagonists

Emerging treatments for alcohol dependence reveal an intricate interplay of neurobiological, psychological, and circumstantial factors that contribute to Alcohol Use Disorder (AUD). The approved strategies balancing these factors involve extensive manipulations of neurotransmitter systems such as GABA, Glutamate, Dopamine, Serotonin, and Acetylcholine. Innovative developments are engaging mechanisms such as GABA reuptake inhibition and allosteric modulation. Closer scrutiny is placed on the role of Glutamate in chronic alcohol consumption, with treatments like NMDA receptor antagonists and antiglutamatergic medications showing significant promise...

Uncontrollable stress exposure impairs working memory and reduces the firing of dorsolateral prefrontal cortex (dlPFC) "Delay cells", involving high levels of norepinephrine and dopamine release. Previous work has focused on catecholamine actions on dlPFC pyramidal cells, but inhibitory interneurons may contribute as well. The current study combined immunohistochemistry and multi-scale microscopy with iontophoretic physiology and behavioral analyses to examine the effects of beta1-noradrenergic receptors (β1-ARs) on inhibitory neurons in layer III dlPFC...

Achieving optimal treatment outcomes for individuals living with schizophrenia remains challenging, despite 70 years of drug development efforts. Many chemically distinct antipsychotics have been developed over the past seven decades with improved safety and tolerability but with only slight variation in efficacy. All currently prescribed antipsychotics act as antagonists or partial agonists at the dopamine D2 receptor. With only a few possible exceptions, antipsychotic drugs have similar and modest efficacy for treating positive symptoms and are relatively ineffective in addressing the negative and cognitive symptoms of the disease...

Dopamine's role as the principal neurotransmitter in motor functions has long been accepted. We broaden this conventional perspective by demonstrating the involvement of non-dopaminergic mechanisms. In mouse models of Parkinson's Disease (PD), we observed that L-DOPA elicited a substantial motor response even when its conversion to dopamine was blocked by inhibiting the enzyme aromatic amino acid decarboxylase (AADC). Remarkably, the motor activity response to L-DOPA in the presence of an AADC inhibitor (NSD1015) showed a delayed onset, yet greater intensity and longer duration, peaking at 7 hours, compared to when L-DOPA was administered alone...

Schizophrenia is a disease with a complex pathological mechanism that is influenced by multiple genes. The study of its pathogenesis is dominated by the dopamine hypothesis, as well as other hypotheses such as the 5-hydroxytryptamine hypothesis, glutamate hypothesis, immune-inflammatory hypothesis, gene expression abnormality hypothesis, and neurodevelopmental abnormality hypothesis. The first generation of antipsychotics was developed based on dopaminergic receptor antagonism, which blocks dopamine D2 receptors in the brain to exert antipsychotic effects...

BACKGROUND: Although dopaminergic disturbances are well-known in schizophrenia, the understanding of dopamine-related brain dynamics remains limited. This study investigates the dynamic coactivation patterns (CAPs) associated with the substantia nigra (SN), a key dopaminergic nucleus, in first-episode treatment-naïve patients with schizophrenia (FES). METHODS: Resting-state fMRI data were collected from 84 FES and 94 healthy controls (HCs). Frame-wise clustering was implemented to generate CAPs related to SN activation or deactivation...

Levodopa-induced dyskinesia (LID) is a common complication in patients with advanced Parkinson's disease (PD) undergoing treatment with levodopa. Glutamate receptor antagonists can suppress LID; however, the underlying mechanisms remain unclear. Here, we aimed to evaluate the effect of 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP), a metabotropic glutamate receptor 5 (mGluR5) antagonist, on dyskinesia. We recorded the neuronal activity of the entopeduncular nucleus and examined responses to cortical electric stimulation in the control group (n = 6) and three groups of rats (male PD model)...

African swine fever virus (ASFV) infection usually causes viremia within a few days. However, the metabolic changes in pig serum after ASFV infection remain unclear. In this study, serum samples collected from ASFV-infected pigs at different times were analyzed using pseudotargeted metabolomics method. Metabolomic analysis revealed the dopaminergic synapse pathway has the highest rich factor in both ASFV5 and ASFV10 groups. By disrupting the dopamine synaptic pathway, dopamine receptor antagonists inhibited ASFV replication and L-dopa promoted ASFV replication...

Acromegaly and gigantism are disorders caused by hypersecretion of growth hormone (GH), usually from pituitary adenomas. Although somatostatin analogues (SSA), dopamine agonists and GH receptor antagonist are important therapeutic agents, all of these have issues with their effectiveness, safety, and/or convenience of use. To overcome these, we developed a GH-specific potent neutralizing mouse monoclonal antibody (mAb) named 13H02. 13H02 selectively bound to both human and monkey GH with high affinity, and strongly inhibited the biological activity of GH in the Nb2 rat lymphoma cell proliferation assay...

BACKGROUND: Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, have emerged as promising therapies for TD and several clinical trials have shown their efficacy. This study aims to compare the efficacy and safety profile of VMAT2 inhibitors, focusing on a recent trial conducted in the Asian population. METHODS: We reviewed the PubMed, Cochrane Library, Embase database, and clinicaltrials...

Activation of the cAMP pathway is one of the common mechanisms underlying long-term potentiation (LTP). In the Drosophila mushroom body, simultaneous activation of odour-coding Kenyon cells (KCs) and reinforcement-coding dopaminergic neurons activates adenylyl cyclase in KC presynaptic terminals, which is believed to trigger synaptic plasticity underlying olfactory associative learning. However, learning induces long-term depression (LTD) at these synapses, contradicting the universal role of cAMP as a facilitator of transmission...

G protein-coupled receptors show preference for G protein subtypes but can recruit multiple G proteins with various downstream signaling cascades. This functional selection can guide drug design. Dopamine receptors are both stimulatory (D1 -like) and inhibitory (D2 -like) with diffuse expression across the central nervous system. Functional selectivity of G protein subunits may help with dopamine receptor targeting and their downstream effects. Three bioluminescence-based assays were used to characterize G protein coupling and function with the five dopamine receptors...

Amphetamine (AMPH) exposure induces behavioural and neurochemical sensitization observed in rodents as hyperlocomotion and increased dopamine release in response to a subsequent dose. Brain Angiotensin II modulates dopaminergic neurotransmission through its AT1 receptors (AT1 -R), positively regulating striatal dopamine synthesis and release. This work aims to evaluate the AT1 -R role in the development and maintenance of AMPH-induced sensitization. Also, the AT1 -R involvement in striatal dopamine reuptake was analysed...

No antiviral drugs currently are available for treatment of infection by hepatitis A virus (HAV), a causative agent of acute hepatitis, a potentially life-threatening disease. Chemical screening of a small-compound library using nanoluciferase-expressing HAV identified loxapine succinate, a selective dopamine receptor D2 antagonist, as a potent inhibitor of HAV propagation in vitro. Loxapine succinate did not inhibit viral entry nor internal ribosome entry site (IRES)-dependent translation, but exhibited strong inhibition of viral RNA replication...

We aimed to investigate the roles of dopamine in regulating caste-specific behaviors in bumble bees and mating-related behaviors in bumble bee gynes. We examined caste differences in behaviors, biogenic amine levels, and expression levels of genes encoding dopamine receptors in the brains of bumble bees, and analyzed the effects of dopamine-related drugs on bumble bee behavior. Locomotor and flight activities were significantly higher in 8-day-old gynes and light avoidance was significantly lower in 4-8-day-old gynes than in same-aged workers...

INTRODUCTION: TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness.6 It is a dopamine (DA) receptor agonist and a N-Methyl-D-aspartate (NMDA) receptor antagonist via dopamine release and dopamine reuptake inhibition...

Bupropion is a substituted cathinone (β-keto amphetamine) norepinephrine/dopamine reuptake inhibitor andnoncompetitive nicotinic acetylcholine receptor antagonist that is frequently used to treat major depressive disorder. Bupropion overdose can cause neurotoxicity and cardiotoxicity, the latter of which is thought to be secondary to gap junction inhibition and ion channel blockade. We report a patient with a confirmed bupropion ingestion causing severe cardiotoxicity, for whom prophylactic veno-arterial extracorporeal membrane oxygenation (ECMO) was successfully implemented...

PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding the use of Solriamfetol for excessive daytime sleepiness. It covers the background and current therapeutic approaches to treating excessive daytime sleepiness, the management of common comorbidities, and the existing evidence investigating the use of Solriamfetol for this purpose. RECENT FINDINGS: Excessive daytime sleepiness leads to worse quality of life, a medical sequela and significant economic cost...

BACKGROUND/AIMS: We examined the involvement of cholecystokinin (CCK) in the exacerbation of indomethacin (IND)-induced gastric antral ulcers by gastroparesis caused by atropine or dopamine in mice. METHODS: Male mice were fed for 2 h (re-feeding) following a 22-h fast. Indomethacin (IND; 10 mg/kg, s.c.) was administered after re-feeding; gastric lesions were examined 24 h after IND treatment. In another experiment, mice were fed for 2 h after a 22-h fast, after which the stomachs were removed 1...

Purinergic dysfunctions are associated with mania and depression pathogenesis. P2X7 receptor (P2X7R) mediates the IL-1β maturation via NLRP3 inflammasome activation. We tested in a mouse model of the subchronic amphetamine (AMPH)-induced hyperactivity whether P2X7R inhibition alleviated mania-like behavior through IL-1β. Treatment with JNJ-47965567, a P2X7R antagonist, abolished AMPH-induced hyperlocomotion in wild-type and IL-1α/β-knockout male mice. The NLRP3 inhibitor MCC950 failed to reduce AMPH-induced locomotion in WT mice, whereas the IL-1 receptor antagonist anakinra slightly increased it...