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Neurogastroenterology and Motility May 2021Dopamine receptor 2 (DRD2) and ghrelin receptor (GHSR1a) agonists both stimulate defecation by actions at the lumbosacral defecation center. Dopamine is in nerve...
BACKGROUND
Dopamine receptor 2 (DRD2) and ghrelin receptor (GHSR1a) agonists both stimulate defecation by actions at the lumbosacral defecation center. Dopamine is in nerve terminals surrounding autonomic neurons of the defecation center, whereas ghrelin is not present in the spinal cord. Dopamine at D2 receptors generally inhibits neurons, but at the defecation center, its effect is excitatory.
METHODS
In vivo recording of defecation and colorectal propulsion was used to investigate interaction between DRD2 and GHSR1a. Localization studies were used to determine sites of receptor expression in rat and human spinal cord.
KEY RESULTS
Dopamine, and the DRD2 agonist, quinpirole, directly applied to the lumbosacral cord, caused defecation. The effect of intrathecal dopamine was inhibited by the GHSR1a antagonist, YIL781, given systemically, but YIL781 was not an antagonist at DRD2. The DRD2 agonist, pramipexole, administered systemically caused colorectal propulsion that was prevented when the pelvic nerves were cut. Drd2 and Ghsr were expressed together in autonomic preganglionic neurons at the level of the defecation centers in rat and human. Behaviorally induced defecation (caused by water avoidance stress) was reduced by the DRD2 antagonist, sulpiride. We had previously shown it is reduced by YIL781.
CONCLUSIONS AND INFERENCES
Our observations imply that dopamine is a transmitter of the defecation pathways whose actions are exerted through interacting dopamine (D2) and ghrelin receptors on lumbosacral autonomic neurons that project to the colorectum. The results explain the excitation by dopamine agonists and the conservation of GHSR1a in the absence of ghrelin.
Topics: Animals; Defecation; Dopamine; Dopamine Agonists; Dopamine Antagonists; Gastrointestinal Motility; Ghrelin; Humans; Piperidines; Pramipexole; Quinazolinones; Quinpirole; Rats; Receptors, Dopamine D2; Receptors, Ghrelin; Spinal Cord; Spinal Cord Lateral Horn; Sulpiride
PubMed: 33264473
DOI: 10.1111/nmo.14051 -
Neurogastroenterology and Motility Nov 2019Metoclopramide is primarily a dopamine receptor antagonist, with 5HT receptor antagonist and 5HT receptor agonist activity, and used as an antiemetic and... (Review)
Review
BACKGROUND
Metoclopramide is primarily a dopamine receptor antagonist, with 5HT receptor antagonist and 5HT receptor agonist activity, and used as an antiemetic and gastroprokinetic since almost 50 years. Regulatory authorities issued restrictions and recommendations regarding long-term use of the drug at oral doses exceeding 10 mg 3-4 times daily because of the risk for development of tardive dyskinesia. The aim of our study was to review mechanism(s) of action and pharmacokinetic-pharmacodynamic properties of metoclopramide, as well as the risk of metoclopramide-induced tardive dyskinesia, factors that may change drug exposure in humans, and to summarize the clinical context for appropriate use of the drug.
METHODS
A PubMed, Google Scholar, and Cross Reference search was done using the key words and combined searches: drug-drug interaction, gastroparesis, metoclopramide, natural history, pharmacokinetics, pharmacodynamics, drug-drug interaction, outcome, risk factors, tardive dyskinesia.
KEY RESULTS
Data show that the risk of tardive dyskinesia from metoclopramide is low, in the range of 0.1% per 1000 patient years. This is far below a previously estimated 1%-10% risk suggested in treatment guidelines by regulatory authorities. High-risk groups are elderly females, diabetics, patients with liver or kidney failure, and patients with concomitant antipsychotic drug therapy, which reduces the threshold for neurological complications.
CONCLUSIONS & INFERENCES
The risk of tardive dyskinesia due to metoclopramide is far below approximated numbers in treatment guidelines. This risk and the influence of known risk factors should be considered when starting a course of metoclopramide for treatment of gastroparesis.
Topics: Antiemetics; Dopamine D2 Receptor Antagonists; Gastroparesis; Humans; Metoclopramide; Risk Factors; Tardive Dyskinesia
PubMed: 31050085
DOI: 10.1111/nmo.13617 -
Current Neurology and Neuroscience... May 2020Pediatric migraine is common, and appropriate abortive treatment is important to limit impact on school performance and mental health. This review will describe the... (Review)
Review
PURPOSE OF REVIEW
Pediatric migraine is common, and appropriate abortive treatment is important to limit impact on school performance and mental health. This review will describe the latest evidence for abortive treatment in the emergency department and inpatient settings.
RECENT FINDINGS
It is recognized that a protocol for emergency department treatment can increase efficacy and prevent admissions. These protocols commonly include a non-opioid analgesic and dopamine receptor antagonist. A novel approach to treatment with valproic acid is use of a continuous infusion. Administration of ketamine or propofol and peripheral nerve blocks could add more expedited treatment options to the armamentarium for pediatric migraine. There is increasing variety in the abortive treatment of pediatric migraine, but continued research is necessary for validation of these approaches.
Topics: Adolescent; Child; Dopamine Antagonists; Emergency Service, Hospital; Headache; Humans; Inpatients; Migraine Disorders
PubMed: 32410204
DOI: 10.1007/s11910-020-01035-5 -
ELife Nov 2021Theoretical accounts distinguish between motivational ('wanting') and hedonic ('liking') dimensions of rewards. Previous animal and human research linked wanting and... (Randomized Controlled Trial)
Randomized Controlled Trial
Theoretical accounts distinguish between motivational ('wanting') and hedonic ('liking') dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Reducing opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. In contrast, reducing dopaminergic neurotransmission with amisulpride revealed no robust effects on behavior or neural activity. Our findings thus provide insights into how opioid receptors mediate neural connectivity related to specifically motivational, not hedonic, aspects of rewards.
Topics: Adult; Amisulpride; Corpus Striatum; Dopamine Antagonists; Dorsolateral Prefrontal Cortex; Double-Blind Method; Female; Healthy Volunteers; Humans; Magnetic Resonance Imaging; Male; Motivation; Naltrexone; Narcotic Antagonists; Reward
PubMed: 34761749
DOI: 10.7554/eLife.71077 -
Frontiers in Neuroscience 2020Stuttering is a DSM V psychiatric condition for which there are no FDA-approved medications for treatment. A growing body of evidence suggests that dopamine antagonist... (Review)
Review
Stuttering is a DSM V psychiatric condition for which there are no FDA-approved medications for treatment. A growing body of evidence suggests that dopamine antagonist medications are effective in reducing the severity of stuttering symptoms. Stuttering shares many similarities to Tourette's Syndrome in that both begin in childhood, follow a similar male to female ratio of 4:1, respond to dopamine antagonists, and symptomatically worsen with dopamine agonists. In recent years, advances in the neurophysiology of stuttering have helped further guide pharmacological treatment. A newer medication with a novel mechanism of action, selective D1 antagonism, is currently being investigated in FDA trials for the treatment of stuttering. D1 antagonists possess different side-effect profiles than D2 antagonist medications and may provide a unique option for those who stutter. In addition, VMAT-2 inhibitors alter dopamine transmission in a unique mechanism of action that offers a promising treatment avenue in stuttering. This review seeks to highlight the different treatment options to help guide the practicing clinician in the treatment of stuttering.
PubMed: 32292321
DOI: 10.3389/fnins.2020.00158 -
Naunyn-Schmiedeberg's Archives of... Jan 2020Repeated administration of stimulants induces conditioned place preference (CPP). Dopamine receptor supersensitivity is developed in stimulant-induced CPP animals;...
Repeated administration of stimulants induces conditioned place preference (CPP). Dopamine receptor supersensitivity is developed in stimulant-induced CPP animals; however, dopamine receptor subtypes associated with the development of supersensitivity in CPP animals are largely unknown. The present preclinical study aimed to examine whether dopamine D1 or D2 receptor antagonists exert inhibitory effects on stimulant-induced psychological behaviors. Additionally, the authors aimed to elucidate the role of dopamine receptor supersensitivity on the development of reward-related behavior. Sprague Dawley rats subjected to methamphetamine- and cocaine-induced CPP tests were treated with dopamine D1 (SCH23390) or D2 (sulpiride) receptor antagonists. Following the CPP experiment, rats were challenged with apomorphine (dopamine receptor agonist), and locomotor activity was measured. Methamphetamine- and cocaine-induced CPP was reduced with the administration of SCH23390, but not sulpiride. In addition, the apomorphine challenge evoked an increase in locomotor activity in stimulant-pre-treated rats, reflecting dopamine receptor supersensitivity. SCH23390 pre-treatment inhibited the development of dopamine receptor supersensitivity, while sulpiride demonstrated no inhibitory effects. These results suggest that the dopamine D1 receptor antagonist SCH23390 inhibits the development of dopamine receptor supersensitivity which is associated with the development of CPP.
Topics: Animals; Benzazepines; Central Nervous System Stimulants; Cocaine; Conditioning, Psychological; Dopamine Antagonists; Locomotion; Male; Methamphetamine; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Sulpiride
PubMed: 31372696
DOI: 10.1007/s00210-019-01694-3 -
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 -
Biotechnology Journal Jun 2022Electrical stimulation of brain or muscle activities has gained attention for studying the molecular and cellular mechanisms involved in electric-induced responses. We...
Electrical stimulation of brain or muscle activities has gained attention for studying the molecular and cellular mechanisms involved in electric-induced responses. We recently showed zebrafish's response to electricity. Here, we hypothesized that this response is affected by the dopaminergic signaling pathways. The effects of multiple dopamine agonists and antagonists on the electric response of 6 days-postfertilization zebrafish larvae were investigated using a microfluidic device with enhanced control of experimentation and throughput. All dopamine antagonists decreased locomotor activities, while dopamine agonists did not induce similar behaviors. The D2-selective dopamine agonist quinpirole enhanced the movement. Exposure to nonselective and D1-selective dopamine agonists apomorphine and SKF-81297 caused no significant change in the electric response. Exposing larvae that were pretreated with nonselective and D2-selective dopamine antagonists butaclamol and haloperidol to apomorphine and quinpirole, respectively, restored the electric locomotion. These results reveal a correlation between electric response and dopamine signaling pathway. Furthermore, they demonstrate that electric-induced zebrafish larvae locomotion can be conditioned by modulating dopamine receptor functions. Our electrofluidic assay has profound application potential for fundamental electric-induced response research and brain disorder studies especially those related to the dopamine imbalance and as a chemical screening method when investigating biological pathways and behaviors.
Topics: Animals; Apomorphine; Dopamine; Dopamine Agonists; Dopamine Antagonists; Electricity; Larva; Quinpirole; Signal Transduction; Zebrafish
PubMed: 35332995
DOI: 10.1002/biot.202100561 -
Current Neurology and Neuroscience... Aug 2019Tardive dyskinesia (TD) is caused by exposure to medications with dopamine antagonism, mainly antipsychotics. It often distresses individuals, physically and emotionally... (Review)
Review
PURPOSE OF REVIEW
Tardive dyskinesia (TD) is caused by exposure to medications with dopamine antagonism, mainly antipsychotics. It often distresses individuals, physically and emotionally and affects their quality of life. We evaluated peer-reviewed recently published articles with a goal of providing a critically appraised update on the latest advancements in this field.
RECENT FINDINGS
In 2017, FDA approved VMAT2 inhibitors, deutetrabenazine and valbenazine. They have demonstrated efficacy in several class 1 studies. Also there have been update in the evidence-based guidelines for treatment for tardive dyskinesia. Various medication classes are being used for treatment of TD with VMAT2 inhibitors to be first FDA-approved medications. Their use should be tailored to the individual patient. Long-term studies will further guide us in how to optimize treatment, especially in the real-world setting. As clinicians, we need to take into consideration all aspects of symptomatology, etiology, potential side effects of the medications, to find the best possible "match" for our patients.
Topics: Antipsychotic Agents; Dopamine Antagonists; Drug-Related Side Effects and Adverse Reactions; Humans; Quality of Life; Tardive Dyskinesia; Tetrabenazine; Valine; Vesicular Monoamine Transport Proteins
PubMed: 31420757
DOI: 10.1007/s11910-019-0976-1 -
Journal of Pain & Palliative Care... Mar 2024Symptoms of nausea and vomiting are common in palliative care and hospice patients. One of the many classes of medications used for the treatment of nausea and vomiting... (Review)
Review
Symptoms of nausea and vomiting are common in palliative care and hospice patients. One of the many classes of medications used for the treatment of nausea and vomiting is dopamine receptor antagonists which are particularly helpful for treating nausea mediated by the chemoreceptor trigger zone (CTZ) and impaired gastrointestinal function. While dopamine antagonists can be very effective treatments for nausea they should be used with caution as they carry the risk of QTc prolongation, have a FDA black box warning for tardive dyskinesia (TD), and increased risk of precipitating psychosis and death in patients with dementia. This review will cover haloperidol, olanzapine, prochlorperazine, and metoclopramide for treatment of nausea and vomiting including evidence of efficacy, pharmacokinetics, and pharmacodynamics to improve safe and effective utilization in clinical practice. This includes medication receptor site affinities at histaminic, muscarinic, serotonergic, and alpha-adrenergic receptors which can help providers anticipate potential adverse effects and risk of extrapyramidal symptoms (EPS), TD, and QTc prolongation. This review also includes considerations for dose adjustments based on renal function, hepatic function, and age. Understanding the pharmacology of dopamine antagonists can help providers choose the best treatment for control of nausea and vomiting and subsequently improve patients' quality of life.
Topics: Humans; Dopamine Antagonists; Palliative Care; Quality of Life; Vomiting; Nausea; Long QT Syndrome
PubMed: 37843383
DOI: 10.1080/15360288.2023.2268065