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CMAJ : Canadian Medical Association... Sep 1986Domperidone is a dopamine antagonist that has recently been released in Canada. Unlike metoclopramide hydrochloride, the other available dopamine antagonist, it does not... (Clinical Trial)
Clinical Trial Review
Domperidone is a dopamine antagonist that has recently been released in Canada. Unlike metoclopramide hydrochloride, the other available dopamine antagonist, it does not readily enter the central nervous system. Domperidone acts as both an antiemetic and an upper gastrointestinal tract prokinetic agent. It is rapidly absorbed after oral administration, and few side effects have been reported. Domperidone has been approved for use in Canada for the symptomatic management of upper gastrointestinal tract motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist agents in Parkinson's disease. The pharmacologic features, indications and side effects of domperidone are reviewed.
Topics: Administration, Oral; Adult; Child; Clinical Trials as Topic; Domperidone; Dopamine Antagonists; Dyspepsia; Gastroesophageal Reflux; Gastrointestinal Motility; Headache; Humans; Infant; Migraine Disorders; Nausea; Parkinson Disease; Stomach Diseases; Tablets; Vomiting
PubMed: 3527396
DOI: No ID Found -
The Journal of Clinical Psychiatry Dec 2019Tardive dyskinesia (TD), a condition of potentially irreversible abnormal involuntary movements that is associated with dopamine receptor blocking agents (DRBAs),... (Review)
Review
Tardive dyskinesia (TD), a condition of potentially irreversible abnormal involuntary movements that is associated with dopamine receptor blocking agents (DRBAs), produces significant impairment of functioning and quality of life for patients. Contrary to expectations, TD has not vanished despite the introduction of SGAs. Instead, changing prescription practices and increased off-label prescription of DRBAs have placed more patients than ever at risk of this potentially dangerous and disabling condition. This activity provides an overview of treatment strategies for TD as part of an individualized management plan, including DRBA medication adjustment and antidyskinetic treatment.
Topics: Antipsychotic Agents; Dopamine Antagonists; Humans; Tardive Dyskinesia
PubMed: 31880872
DOI: 10.4088/JCP.NU18041BR4C -
Behavioural Neurology 2013Huntington disease (HD) is an inherited neuropsychiatric condition with progressive neurodegenerative changes, mainly affecting the striatum. Pathological processes... (Review)
Review
BACKGROUND
Huntington disease (HD) is an inherited neuropsychiatric condition with progressive neurodegenerative changes, mainly affecting the striatum. Pathological processes within the striatum are likely to lead to alterations in dopamine and glutamate activity in frontostriatal circuitry, resulting in characteristic motor, behavioural and cognitive symptoms.
METHODS
We conducted a systematic literature search in order to identify and review randomised, double-blinded, placebo-controlled trials of anti-dopaminergic and anti-glutamatergic therapy in HD.
RESULTS
Ten studies satisfied our selection criteria. These studies investigated a range of agents which act to antagonise dopamine (tetrabenazine, typical and atypical antipsychotics) or glutamate (amantadine, riluzole) transmission.
DISCUSSION
Although most agents showed efficacy in terms of amelioration of chorea, the available evidence did not allow us to identify a universally effective treatment. One difficulty associated with analysing the available evidence was a high prevalence of side effects, which prevented the full therapeutic potential of the medications from being adequately investigated. A further limitation is that many studies evaluated treatment effectiveness only in relation to patients' motor symptoms, even though behavioural and cognitive changes may negatively impact patients' quality of life. There is a clear need for further higher-level evidence addressing the effects of dopaminergic and glutamatergic agents on global functioning in HD.
Topics: Brain; Dopamine; Dopamine Antagonists; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Huntington Disease
PubMed: 22713410
DOI: 10.3233/BEN-2012-120268 -
Physiology & Behavior Jul 2011An early study performed in Bart Hoebel's laboratory suggested that dopamine (DA) signaling in the nucleus accumbens was involved in learned flavor preferences produced... (Review)
Review
An early study performed in Bart Hoebel's laboratory suggested that dopamine (DA) signaling in the nucleus accumbens was involved in learned flavor preferences produced by post-oral nutritive feedback. This paper summarizes our studies investigating the role of DA in flavor preference conditioning using selective DA receptor antagonists. Food-restricted rats were trained to prefer a flavored saccharin solution (CS+) paired with intragastric (IG) sugar infusions over a flavored saccharin solution (CS-) paired with water infusions. Systemic injections of a D1-like receptor antagonist (SCH23390), but not a D2-like receptor antagonist (raclopride) during training blocked flavor preference learning. Neither drug prevented the expression of an already learned preference except at high doses that greatly suppressed total intakes. Central sites of action were examined by local microinjections of SCH23390 (12 nmol) during flavor training or testing. Drug infusions in the nucleus accumbens, amygdala, medial prefrontal cortex, or lateral hypothalamus during training blocked or attenuated CS+ flavor conditioning by IG glucose infusions. The same drug dose did not suppress the expression of a learned CS+ preference. The findings suggest that DA signaling within different components of a distributed brain network is involved in sugar-based flavor preferences. A possible role of DA in conditioned increases in flavor acceptance is discussed.
Topics: Animals; Dopamine; Dopamine Antagonists; Food Preferences; Learning; Nucleus Accumbens; Rats; Receptors, Dopamine; Reward; Saccharin
PubMed: 21549727
DOI: 10.1016/j.physbeh.2011.04.039 -
Behavioral Neuroscience Dec 2009Experimentally induced and parkinsonian disruptions in dopamine (DA) transmission are associated with motor abnormalities that include a reduced likelihood of behavioral...
Experimentally induced and parkinsonian disruptions in dopamine (DA) transmission are associated with motor abnormalities that include a reduced likelihood of behavioral response initiation and an increased duration of executed responses. Here we investigated the dopamine receptor subtypes involved in regulating these two aspects of behavior. We examined the effects of D1 family (D1/D5) antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0, 0.04, 0.08, or 0.16 mg/kg) and D2/D3 antagonist 3,5-dichloro-N-(1-ethylpyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxybenzamide (+)-tartrate salt (raclopride; 0, 0.2, or 0.4 mg/kg) on the likelihood and duration of a cued Pavlovian approach and a cued operant lever-press response. While the high doses of the D1 and D2 antagonists produced similar levels of overall locomotor suppression, only the D2 antagonist increased the duration of time that animals' heads remained in the food compartment during both Pavlovian and operant task performance. In contrast, D1 antagonist SCH23390 decreased the proportion of trials in which animals executed both the Pavlovian approach and operant lever-press, while raclopride did not. The results suggest that D2 receptor blockade preferentially increases response duration, and, under the simple discrete-trial procedures employed here, D1 receptor blockade preferential reduces Pavlovian and operant response likelihood.
Topics: Analysis of Variance; Animals; Benzazepines; Conditioning, Classical; Conditioning, Operant; Cues; Dopamine Antagonists; Dose-Response Relationship, Drug; Male; Motor Activity; Raclopride; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 20001111
DOI: 10.1037/a0017702 -
Biomedicine & Pharmacotherapy =... Jan 2022Dopamine (DA) is a crucial neurotransmitter that plays an important role in maintaining physiological function in human body. In the past, most studies focused on the... (Review)
Review
Dopamine (DA) is a crucial neurotransmitter that plays an important role in maintaining physiological function in human body. In the past, most studies focused on the relationship between the dopaminergic system and neurological-related diseases. However, it has been found recently that DA is an immunomodulatory mediator and many immune cells express dopamine receptors (DRs). Some immune cells can synthesize and secrete DA and then participate in regulating immune function. DRs agonists or antagonists can improve the dysfunction of immune system through classical G protein signaling pathways or other non-receptor-dependent pathways. This article will discuss the relationship between the dopaminergic system and the immune system. It will also review the use of DRs agonists or antagonists to treat chronic and acute inflammatory diseases and corresponding immunomodulatory mechanisms.
Topics: Central Nervous System; Dopamine; Dopamine Agonists; Dopamine Antagonists; Humans; Immune System; Immunologic Factors; Neurotransmitter Agents; Signal Transduction
PubMed: 34847478
DOI: 10.1016/j.biopha.2021.112458 -
Comparative Biochemistry and... Oct 2022Chelonoidis carbonaria aortic rings present endothelium-derived release of dopamine, noradrenaline, adrenaline and 6-nitrodopamine (6-ND). Here it was investigated...
Chelonoidis carbonaria aortic rings present endothelium-derived release of dopamine, noradrenaline, adrenaline and 6-nitrodopamine (6-ND). Here it was investigated whether 6-ND release is coupled to nitric oxide (NO) synthesis and its action on the vascular smooth muscle reactivity. Basal release of 6-ND from aortic rings in the absence and presence of the NO synthesis inhibitor L-NAME was quantified by LC-MS-MS. Aortic rings were suspended vertically between two metal hooks in 10-mL organ baths containing Krebs-Henseleit's solution and attached to isometric transducers. The tissues were allowed to equilibrate for 1 h before starting the experiments. The release of 6-ND was significantly reduced by previous incubation with L-NAME. 6-ND (up to 300 μM) had no contractile activity in the aortic rings. 6-ND (1, 3 and 10 μM) produced significant rightward shifts of the concentration-response curves to dopamine in endothelium-intact (pA 6.09) and L-NAME pre-treated endothelium-intact (pA 7.06) aortic rings. Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND. The EFS (16 Hz)-induced aortic contractions were significantly inhibited by incubation with 6-ND (10 μM). In the thromboxane A mimetic U-46619 (30 nM) pre-contracted endothelium intact aortic rings, 6-ND (1 nM-1 μM) and the dopamine D-receptor antagonist haloperidol (1 nM-1 μM) induced concentration-dependent relaxations. The relaxations were not present in endothelium-removed aortic rings but they were not affected by incubation with L-NAME in endothelium-intact aortic rings. The results indicate that the synthesis of this novel catecholamine in Chelonoidis carbonaria aortic rings is coupled to NO release and that 6-ND acts as a highly selective dopamine D-like receptor antagonist.
Topics: Animals; Aorta; Aorta, Thoracic; Dopamine; Dopamine Antagonists; Epinephrine; NG-Nitroarginine Methyl Ester; Nitric Oxide; Norepinephrine; Turtles
PubMed: 35793735
DOI: 10.1016/j.cbpc.2022.109403 -
European Neuropsychopharmacology : the... Aug 2013Currently available treatments have limited pro-cognitive effects for neuropsychiatric disorders, such as schizophrenia, Parkinson's disease and Alzheimer's disease. The... (Review)
Review
Currently available treatments have limited pro-cognitive effects for neuropsychiatric disorders, such as schizophrenia, Parkinson's disease and Alzheimer's disease. The primary objective of this work is to review the literature on the role of dopamine D₃ receptors in cognition, and propose dopamine D₃ receptor antagonists as possible cognitive enhancers for neuropsychiatric disorders. A literature search was performed to identify animal and human studies on D₃ receptors and cognition using PubMed, MEDLINE and EMBASE. The search terms included "dopamine D₃ receptor" and "cognition". The literature search identified 164 articles. The results revealed: (1) D₃ receptors are associated with cognitive functioning in both healthy individuals and those with neuropsychiatric disorders; (2) D₃ receptor blockade appears to enhance while D₃ receptor agonism seems to impair cognitive function, including memory, attention, learning, processing speed, social recognition and executive function independent of age; and (3) D₃ receptor antagonists may exert their pro-cognitive effect by enhancing the release of acetylcholine in the prefrontal cortex, disinhibiting the activity of dopamine neurons projecting to the nucleus accumbens or prefrontal cortex, or activating CREB signaling in the hippocampus. These findings suggest that D₃ receptor blockade may enhance cognitive performance in healthy individuals and treat cognitive dysfunction in individuals with a neuropsychiatric disorder. Clinical trials are needed to confirm these effects.
Topics: Animals; Cognition; Cognition Disorders; Dopamine Antagonists; Humans; Mental Disorders; Molecular Targeted Therapy; Nerve Tissue Proteins; Neurons; Performance-Enhancing Substances; Prefrontal Cortex; Receptors, Dopamine D3; Synaptic Transmission
PubMed: 23791072
DOI: 10.1016/j.euroneuro.2013.05.006 -
Alimentary Pharmacology & Therapeutics Jan 2010Metoclopramide is a dopamine receptor antagonist which has been used for treatment of a variety of gastrointestinal symptoms over the last thirty years. In 2009, the FDA... (Review)
Review
BACKGROUND
Metoclopramide is a dopamine receptor antagonist which has been used for treatment of a variety of gastrointestinal symptoms over the last thirty years. In 2009, the FDA issued a black box warning regarding long-term or high-dose use of this medication because of the risk of developing tardive dyskinesia.
AIMS
To review the mechanism of action and pharmacokinetic properties of metoclopramide, the risk of metoclopramide-induced tardive dyskinesia, potential mechanisms that may alter and to summarize the clinical context for appropriate use of the drug.
METHODS
We conducted a PubMed search using the following key words and combined searches: metoclopramide, neuroleptics, tardive dyskinesia, incidence, prevalence, dopamine, receptors, pharmacokinetic, pharmacology, pharmacogenetics, DRD3 Ser9Gly polymorphism, cytochrome P450, p-glycoprotein, risk factors, gastroparesis, outcome, natural history.
RESULTS
Available data show that risk of tardive dyskinesia from metoclopramide use is likely to be <1%, much less than the estimated 1-10% risk previously suggested in national guidelines. Tardive dyskinesia may represent an idiosyncratic response to metoclopramide; pharmacogenetics affect pharmacokinetic and dopamine receptor pharmacodynamics in response to neuroleptic agents that cause similar neurological complications.
CONCLUSION
Community prevalence and pharmacogenetic mechanisms involved in metoclopramide-induced tardive dyskinesia require further study to define the benefit-risk ratio more clearly.
Topics: Dopamine Antagonists; Dyskinesia, Drug-Induced; Humans; Metoclopramide; Odds Ratio; Prevalence; Risk Factors
PubMed: 19886950
DOI: 10.1111/j.1365-2036.2009.04189.x -
ENeuro 2022The orbitofrontal cortex (OFC) and piriform cortex (Pir) play a role in fentanyl relapse after food choice-induced voluntary abstinence, a procedure mimicking abstinence...
The orbitofrontal cortex (OFC) and piriform cortex (Pir) play a role in fentanyl relapse after food choice-induced voluntary abstinence, a procedure mimicking abstinence because of availability of alternative nondrug rewards. We used hybridization and pharmacology to determine the role of OFC and Pir cannabinoid and dopamine receptors in fentanyl relapse. We trained male and female rats to self-administer food pellets for 6 d (6 h/d) and intravenous fentanyl (2.5 µg/kg/infusion) for 12 d (6 h/d). We assessed fentanyl relapse after 12 discrete choice sessions between fentanyl and food (20 trials/d), in which rats voluntarily reduced fentanyl self-administration. We used RNAscope to determine whether fentanyl relapse is associated with activity (indicated by ) in OFC and Pir cells expressing [which encodes cannabinoid 1 (CB1) receptors] or and (which encode dopamine D1 and D2 receptors). We injected a CB1 receptor antagonist or agonist (0.3 or 1.0 µg AM251 or WIN55,212-2/hemisphere) into OFC or a dopamine D1 receptor antagonist (1.0 or 3.0 µg SCH39166/hemisphere) into Pir to determine the effect on fentanyl relapse. Fentanyl relapse was associated with OFC cells co-expressing and and Pir cells co-expressing and However, injections of the CB1 receptor antagonist AM251 or agonist WIN55,212-2 into OFC or the dopamine D1 receptor antagonist SCH39166 into Pir had no effect on fentanyl relapse. Fentanyl relapse is associated with activation of -expressing OFC cells and -expressing Pir cells, but pharmacological manipulations do not support causal roles of OFC CB1 receptors or Pir dopamine D1 receptors in fentanyl relapse.
Topics: Animals; Cannabinoids; Dopamine; Dopamine Antagonists; Female; Fentanyl; Male; Piriform Cortex; Rats; Receptor, Cannabinoid, CB1; Receptors, Dopamine D1; Recurrence
PubMed: 35768212
DOI: 10.1523/ENEURO.0496-21.2022