Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D₃ receptor (D₃R) have effects on addiction in different animal models. We have previously reported that YQA14, a D₃R antagonist, exhibits very high affinity and selectivity for D₃Rs over D₂Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D₃R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.
Rats ; Mice ; Animals ; Analgesics, Opioid ; Dopamine ; Heroin/pharmacology* ; Dopamine Antagonists/pharmacology* ; Receptors, Dopamine D3/metabolism* ; Morphine/pharmacology* ; Behavior, Addictive/drug therapy* ; Self Administration

Parkinson's disease is one of the most common neurodegenerative disorders world widely. Although curable therapies are practically not available yet, symptomatic managements using anti-Parkinson medications have shown to be quite effective to improve patients' quality of life. The discovery of dopaminergic deficits in Parkinson's disease in 1960s have brought about the human clinical trials of levodopa, which opened an “Era of Dopamine” in treatment history of the Parkinson's disease. Levodopa still remains gold standard. Dopamine agonists have proved their efficacies and delayed the development of long-term complications of levodopa use. Inhibitors of respective enzyme monoamine oxidase-B and catechol-O-methyltransferase, anticholinergics, and amantadine strengthen the therapeutic effects via either monotherapy or adjunctive way. Strategy of continuous dopaminergic stimulation and disease modification are weighing in current advances. This article is providing evidence-based review of pharmacological treatment of Parkinson's disease from early to advanced stages as well as management its unavoidable adverse reactions.
Amantadine ; Catechol O-Methyltransferase ; Cholinergic Antagonists ; Dopamine Agonists ; Drug Therapy ; Humans ; Levodopa ; Neurodegenerative Diseases ; Parkinson Disease ; Quality of Life ; Therapeutic Uses

Pharmacotherapy has been constantly chosen by the clinician among the available treatment options for tinnitus. Medications that have been prescribed off-label to treat tinnitus can be grouped into several categories: benzodiazepines, antidepressants, anticonvulsants, N-methyl-D-aspartate (NMDA) receptor antagonists, dopamine receptor modulators, muscle relaxants, and others. In this article, a wide variety of compounds once used in the treatment of tinnitus and evidenced by clinical trials are reviewed with respect to the mechanisms of action and the drug efficacy. Only a few of the various pharmacological interventions investigated have some beneficial effects against tinnitus: clonazepam, acamprosate, neramexan, and sulpiride. Sertraline and pramipexole were effective in subgroups of patients with psychiatric symptoms or presbycusis. However, no agents have been identified to provide a reproducible long-term reduction of tinnitus in excess of placebo effects. In rodent tinnitus models, L-baclofen, memantine, and KCNQ2/3 channel activators have been demonstrated to reduce tinnitus development. Limitation of the use of an effective high dosage during a longer treatment duration due to dose-dependent side effects of the centrally acting drugs may influence the results in clinical studies. More effective and safer innovative agents should be developed based on the further understanding of tinnitus neural mechanisms and valid animal models, and should be supported by improved clinical trial methodology. The management of tinnitus patients through a tailored treatment approach depending on the detailed classification of tinnitus subtypes will also lead to better treatment outcomes.
Anticonvulsants ; Antidepressive Agents ; Benzodiazepines ; Classification ; Clonazepam ; Dopamine Agonists ; Dopamine Antagonists ; Drug Therapy ; Humans ; Memantine ; Models, Animal ; N-Methylaspartate ; Placebo Effect ; Presbycusis ; Rodentia ; Sertraline ; Sulpiride ; Tinnitus*

Urinary incontinence, although rarely reported, is one of the most important adverse effects of antipsychotic medication. It can be an embarrassing, distressing, and potentially treatment-limiting. Several antipsychotics, including both typical and atypical varieties, are known to induce urinary incontinence. Many antipsychotic drugs target the neural pathways controlling continence by binding to receptors of some neurotransmitters such as serotonin, dopamine, acetylcholine, and adrenaline. Pharmacological management of incontinence should be considered if there is a risk of cessation of the antipsychotic therapy or any decline in patients' compliance. Amitriptyline, desmopressin, ephedrine, and anticholinergics such as oxybutynin and trihexyphenidyl are the most frequently used agents to treat incontinence. We think that the frequency of incontinence is higher than reported in the literature, and that follow-up routines should include a form of standardized screening for all possible adverse effects, including incontinence, of any given antipsychotic. In this article, we report a case of urinary incontinence as an adverse effect of paliperidone palmitate use during maintenance therapy in a patient with schizophrenia.
Acetylcholine ; Amitriptyline ; Antipsychotic Agents ; Cholinergic Antagonists ; Compliance ; Deamino Arginine Vasopressin ; Dopamine ; Ephedrine ; Epinephrine ; Follow-Up Studies ; Humans ; Mass Screening ; Neural Pathways ; Neurotransmitter Agents ; Schizophrenia ; Serotonin ; Trihexyphenidyl ; Urinary Incontinence* ; Paliperidone Palmitate

OBJECTIVETo observe the long-term changes in anxiety-like behavior and tyrosine hydroxylase (TH) expression in the substantia nigra (SN) after hypoxic-ischemic brain damage (HIBD) in a neonatal rat model and to further explore the relationship between dopamine (DA) level and long-term anxiety-like behavior using the DA receptor (DAR) antagonist.

METHODSSeven-day-old (P7) neonatal Sprague-Dawley (SD) rats were randomized into normal control, sham-operated, HIBD and HIBD+DAR antagonist groups. HIBD model was prepared by ligating the right common carotid artery and 8% hypoxia exposure. The rats in the sham-operated group were sham-operated and were not subjected to right common carotid artery ligation and hypoxia exposure. The DAR antagonist was injected intraperitoneally before and after inducing HIBD. The same amount of normal saline was given to the other three groups as a control. Anxiety-like behavior was evaluated by elevated plus maze test, and TH expression in the SN was measured by immunohistochemistry on P14, P21, and P28.

RESULTSOn P21 and P28, the time spent in the open arms and the percentage of open arms entries in the HIBD group were significantly increased compared with those in the normal control, sham-operated and HIBD+DAR antagonist groups (P<0.05); in addition, the HIBD+DAR antagonist group showed a significantly longer time spent in the open arms than the normal control group (P<0.05). On P14, P21, and P28, TH expression in the HIBD and HIBD+DAR antagonist groups was significantly lower than that in the normal control and sham-operated groups, and TH level in the HIBD group was significantly lower than that in the HIBD+DAR antagonist group (P<0.05).

CONCLUSIONSDAR antagonist allows the restoration of anxiety-like behavior and alleviates the damage to dopaminergic neurons in SD rats after HIBD.

Animals ; Animals, Newborn ; Anxiety ; etiology ; prevention & control ; Dopamine Antagonists ; therapeutic use ; Hypoxia-Ischemia, Brain ; complications ; Maze Learning ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine ; physiology ; Substantia Nigra ; enzymology ; Tyrosine 3-Monooxygenase ; analysis

Acamprosate reduces the craving for alcohol by decreasing glutamate activity and increasing gamma-aminobutyric acid (GABA) action in patients with alcohol dependence. Acamprosate has tolerable side effects that include diarrhea, headache, dizziness and pruritus. In this study, we report acamprosate-induced extrapyramidal symptoms in an elderly patient with no history of neurologic disease. Severe extrapyramidal symptoms developed two days after the administration of acamprosate and improved over one week after the acamprosate was stopped. Extrapyramidal symptoms are commonly associated with dopamine receptor antagonists. However, there have been several reports of extrapyramidal symptoms occurring with drugs targeting other systems, including GABA, glutamate and serotonin. Acamprosate may decrease dopamine levels in the ventral tegmental area mediated by glutamatergic action and thus cause extrapyramidal symptoms. We suggest that acamprosate carries the risk of causing extrapyramidal symptoms.
Aged* ; Alcoholism* ; Diarrhea ; Dizziness ; Dopamine ; Dopamine Antagonists ; gamma-Aminobutyric Acid ; Glutamic Acid ; Headache ; Humans ; Pruritus ; Serotonin ; Ventral Tegmental Area

Cardio-renal syndromes are disorders of the heart and kidney wherein acute or long-term dysfunction in one organ may induce acute or long-term dysfunction of the other. Because of this complex organ interaction, management of cardiorenal syndrome must be tailored to the underlying pathophysiology. Clinical guidelines exist for the treatment of heart failure or renal failure as separate conditions. Thus far, however, there has been no consensus about managing patients with cardio-renal and reno-cardiac syndromes. Pharmacologic treatment remains a controversial subject. Standard cardiac drugs such as diuretics and inotropes may have limited effect because resistance often develops after long-term use. Recent studies of patients with acute cardio-renal syndromes have focused on newer therapies, including phosphodiesterase inhibitors, vasopressin antagonists, adenosine A1 receptor antagonists, and renal protective dopamine. Initial clinical trials of these agents have shown encouraging results in some patients with heart failure, but have failed to demonstrate a clear superiority over more conventional treatments. Similarly, the benefits of diuretics, aspirin, erythropoietin agents, and iron supplements for management of chronic cardiorenal syndromes are unknown.
Adenosine A1 Receptor Antagonists ; Aspirin ; Cardio-Renal Syndrome ; Consensus ; Diuretics ; Dopamine ; Erythropoietin ; Heart ; Heart Failure ; Humans ; Iron ; Kidney ; Phosphodiesterase Inhibitors ; Renal Insufficiency ; Vasopressins

The aim of this study was to investigate the outcome, and optimal duration of medical treatment in children with superior mesenteric artery syndrome (SMAS). Eighteen children with SMAS were retrospectively studied. The data reviewed included demographics, presenting symptoms, co-morbid conditions, clinical courses, nutritional status, treatments, and outcomes. The three most common symptoms were postprandial discomfort (67.7%), abdominal pain (61.1%), and early satiety (50%). The median duration of symptoms before diagnosis was 68 days. The most common co-morbid condition was weight loss (50%), followed by growth spurt (22.2%) and bile reflux gastropathy (16.7%). Body mass index (BMI) was normal in 72.2% of the patients. Medical management was successful in 13 patients (72.2%). The median duration of treatment was 45 days. Nine patients (50%) had good outcomes without recurrence, 5 patients (27.8%) had moderate outcomes, and 4 patients (22.2%) had poor outcomes. A time limit of >6 weeks for the duration of medical management tended to be associated with worse outcomes (P=0.018). SMAS often developed in patients with normal BMI or no weight loss. Medical treatment has a high success rate, and children with SMAS should be treated medically for at least 6 weeks before surgical treatment is considered.
Adolescent ; Bile Reflux/diagnosis ; Child ; Child, Preschool ; Demography ; Domperidone/therapeutic use ; Dopamine Antagonists/therapeutic use ; Drug Administration Schedule ; Female ; Histamine H2 Antagonists/therapeutic use ; Humans ; Infant ; Male ; Parenteral Nutrition ; Retrospective Studies ; Superior Mesenteric Artery Syndrome/*diagnosis/drug therapy ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome ; Weight Loss

Schizophrenia (SCZ) is a polygenic, multi-factorial disorder and a definitive understanding of its pathophysiology has been lacking since it was first described more than a century ago. The predominant pharmacological approach used to treat SCZ is the use of dopamine receptor antagonists. The fact that many patients remain symptomatic, despite complying with medication regimens, emphasises the need for a more encompassing explanation for both the causes and treatment of SCZ. Recent neuroanatomical, neurobiological, environmental and genetic studies have revived the idea that inflammatory pathways are involved in the pathogenesis of SCZ. These new insights have emerged from multiple lines of evidence, including the levels of inflammatory proteins in the central nervous system of patients with SCZ and animal models. This review focuses on aberrant inflammatory mechanisms present both before and during the onset of the psychotic symptoms that characterise SCZ and discusses recent research into adjunctive immune system modulating therapies for its more effective treatment.
Central Nervous System ; Dopamine Antagonists ; Humans ; Immune System ; Inflammation ; Models, Animal ; Schizophrenia*

Postoperative nausea and vomiting (PONV) is considered as a main cause of dissatisfaction after surgery with postoperative pain. Overall incidence of PONV is 30%, and the incidence rate can increase up to 70-80% in high-risk patient groups. The causes of PONV are multifactorial and can largely be categorized as patient risk factors, surgical procedure, and anaesthetic technique. Pharmacological treatments including dopamine antagonist, anti-histamines, anticholinergics, dexamethasone, neurokinin-1 antagonists, and serotonin antagonist are used to prevent and treat PONV. This article reviews the prevalence, mechanisms, and risk factors of PONV, and how to prevent and treat it.
Cholinergic Antagonists ; Dexamethasone ; Dopamine ; Humans ; Incidence ; Pain, Postoperative ; Postoperative Nausea and Vomiting ; Prevalence ; Risk Factors ; Serotonin