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CNS Spectrums Apr 2020In community settings, negative symptoms and cognitive deficits are the primary barriers to independent living, stable relationships, and employment for individuals... (Review)
Review
In community settings, negative symptoms and cognitive deficits are the primary barriers to independent living, stable relationships, and employment for individuals suffering from schizophrenia-spectrum disorders. In contrast, however, positive psychotic symptoms (e.g., command hallucinations and persecutory delusions) often drive behavior which serves as the gateway to arrest and criminalization. Historically, the keystone of treatment for positive psychotic symptoms has been antagonism of dopamine D2 receptors in the mesolimbic tract. In this article, we review and explore the principles underlying dopamine antagonism for the treatment of psychosis; optimization of dopamine antagonists in treating positive psychotic symptoms; the advantages of depot dopamine antagonist antipsychotics in forensic settings; the concepts of pharmacokinetic and pharmacodynamic treatment failures; and the role of medication plasma concentrations in optimizing and managing treatment.
Topics: Antipsychotic Agents; Dopamine Antagonists; Forensic Psychiatry; Humans; Medication Adherence; Schizophrenia; Schizophrenic Psychology
PubMed: 31060635
DOI: 10.1017/S1092852919000841 -
Journal of Clinical Pharmacy and... Feb 2018Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist.
METHODS
A literature review was conducted using MEDLINE, Ovid, Science Direct, Web of Science and Cochrane Database of Systematic Reviews databases with keywords:hypertension, hypotension, renin-angiotensin-aldosterone system, dopaminergic receptors, blood pressure, antipsychotics. Inclusion criteria were human or animal studies, systematic reviews, meta-analyses, randomized controlled trials, case report/series, published in selected for inclusion.
RESULTS AND DISCUSSION
All 5 dopamine receptor subtypes (ie D1, D2, D3, D4 and D5) regulate sodium excretion and BP. The D1, D3 and D4 receptors interact directly with the renin-angiotensin-aldosterone system, whereas D2 and D5 receptors directly interact with the sympathetic nervous system to regulate BP. Use of dopaminergic agonists or antagonists could therefore disturb the regulation of BP by dopamine receptors.
WHAT IS NEW AND CONCLUSION
Based upon this review, individuals on antipsychotic agents, particularly clozapine, should be routinely monitored for hypertension, and addition of antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) is indicated if hypertension occurs.
Topics: Animals; Antihypertensive Agents; Antipsychotic Agents; Blood Pressure; Dopamine Antagonists; Humans; Receptors, Dopamine
PubMed: 29119585
DOI: 10.1111/jcpt.12649 -
Anesthesia and Analgesia Jun 2019
Topics: Administration, Intravenous; Amisulpride; Dopamine Antagonists; Double-Blind Method; Humans; Postoperative Nausea and Vomiting; Vomiting
PubMed: 31094771
DOI: 10.1213/ANE.0000000000004164 -
Journal of Clinical Psychopharmacology Feb 1995Before the dopamine hypothesis of schizophrenia became established, a serotonin (5-hydroxy-tryptamine) 5-HT hypothesis was popular. This was based on the hallucinogenic... (Review)
Review
Before the dopamine hypothesis of schizophrenia became established, a serotonin (5-hydroxy-tryptamine) 5-HT hypothesis was popular. This was based on the hallucinogenic properties of lysergic acid diethlyamide and abnormal serotonin levels in schizophrenics. Suggestions that serotonin might be involved in the cause of schizophrenia or could be a target for antipsychotic drug action began with the discovery that the antipsychotic agent clozapine is a potent serotonin 5-HT2A antagonist, as well as being a dopamine D2 antagonist. This led to the formulation of the serotonin-dopamine antagonist (SDA) concept for antipsychotics, with wider spectrums of activity and lower extrapyramidal side effects (EPS) liability. The principle of the SDAs is that the drug should be a potent serotonin 5-HT2A antagonist, with slightly less potent dopamine D2 receptor-blocking properties. The clinical experience with risperidone, the first member of the new class of antipsychotics, seems to offer the promise that the SDAs have significant advantages over both the conventional dopamine-blocking neuroleptics and the atypical antipsychotic clozapine. Risperidone has efficacy against both the positive and negative symptoms of schizophrenia and has a low tendency to produce EPS. Only time will tell whether other SDAs will have the same advantages.
Topics: Antipsychotic Agents; Dopamine; Dopamine Antagonists; Humans; Schizophrenia; Serotonin; Serotonin Antagonists
PubMed: 7730499
DOI: 10.1097/00004714-199502001-00002 -
The American Journal of Gastroenterology Sep 2007Domperidone is a dopamine-2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function... (Review)
Review
Domperidone is a dopamine-2 receptor antagonist. It acts as an antiemetic and a prokinetic agent through its effects on the chemoreceptor trigger zone and motor function of the stomach and small intestine. Unlike metoclopramide, it does not cause any adverse neurological symptoms as it has minimal penetration through the blood-brain barrier. It thus provides an excellent safety profile for long-term administration orally in the recommended doses. Domperidone is widely used in many countries and can now be officially prescribed to patients in the United States by an investigational new drug application for the treatment of gastroparesis and any condition causing chronic nausea and vomiting. In view of this additional clinical exposure of domperidone to a new generation of gastroenterologists and other specialists, the purpose of this timely review is to revisit the pharmacology, clinical application, and safety profile of this beneficial medication.
Topics: Antiemetics; Domperidone; Dopamine Antagonists; Gastrointestinal Diseases; Humans; Nausea; Vomiting
PubMed: 17488253
DOI: 10.1111/j.1572-0241.2007.01255.x -
The Journal of General Virology Jun 2022Oncolytic adenoviruses (OAds) have attracted much attention as novel anticancer agents. Numerous studies have examined the antitumour effects of combinational use of an...
Oncolytic adenoviruses (OAds) have attracted much attention as novel anticancer agents. Numerous studies have examined the antitumour effects of combinational use of an OAd and anticancer agents; however, few chemical compounds enhancing OAd infection have been reported. In this study, we screened a food and drug administration (FDA)-approved drug library containing 1134 small chemical compounds to identify chemical compounds that enhance OAd replication in human tumour cells. We found that domperidone, a dopamine D2 receptor antagonist, significantly enhanced the replication of an OAd in human tumour cells, including human pancreatic tumour cells, by two-fivefold, resulting in improvement of OAd-mediated tumour cell killing activities. The E1A mRNA levels were significantly increased in domperidone-pre-treated cells following OAd infection, which contributed to the promotion of OAd replication. However, mRNA levels of the dopamine D2 receptor (DRD2), which is known to be a target molecule of domperidone, were undetectable in most of the tumour cells by real-time reverse transcription (RT)-PCR analysis, indicating that domperidone promoted OAd replication by acting on a molecule other than DRD2. This study provides important clues for the improvement of OAd-mediated cancer therapy.
Topics: Adenoviridae; Adenoviridae Infections; Antineoplastic Agents; Cell Line, Tumor; Domperidone; Dopamine Antagonists; Humans; Oncolytic Virotherapy; Oncolytic Viruses; RNA, Messenger
PubMed: 35731650
DOI: 10.1099/jgv.0.001752 -
American Journal of Health-system... May 1998The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, dosage and administration, and cost of olanzapine are reviewed. Olanzapine is... (Review)
Review
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, dosage and administration, and cost of olanzapine are reviewed. Olanzapine is a serotonin-dopamine-receptor antagonist indicated for use in the treatment of schizophrenia and other psychotic disorders. The affinity of olanzapine for neuroreceptors is similar to that of clozapine. The drug is well absorbed from the GI tract; food has no effect. Olanzapine is more effective than placebo and equal to haloperidol in reducing psychotic symptoms on two rating scales. However, unlike typical dopamine-receptor antagonists used for antipsychotic therapy, olanzapine is more effective in reducing the negative symptoms of schizophrenia. The most frequent adverse drug reactions (ADRs) associated with olanzapine are somnolence, agitation, insomnia, and headache. Constipation and dry mouth occur as dose-dependent ADRs. Unlike clozapine, olanzapine does not cause agranulocytosis. No cases of tardive dyskinesia or neuroleptic malignant syndrome have been reported. Olanzapine has been associated with slight increases in hepatic transaminases. More study is needed to determine whether olanzapine interacts significantly with other drugs. The recommended starting dosage is 5-10 mg orally once daily. Efficacy beyond six weeks has not been evaluated; patients treated for longer than six weeks should be periodically reassessed. Olanzapine costs about 10 times more than typical antipsychotics because a generic version is not available; however, olanzapine costs less than clozapine therapy and may cost less than haloperidol in terms of total health care costs. Olanzapine offers an effective alternative for treating schizophrenia and has a favorable adverse-effect profile.
Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dopamine Antagonists; Humans; Obsessive-Compulsive Disorder; Olanzapine; Pirenzepine; Schizophrenia; Serotonin Antagonists
PubMed: 9606451
DOI: 10.1093/ajhp/55.10.1003 -
The Journal of Experimental Biology Sep 2023Despite lacking a brain and having an apparent symmetrically pentaradial nervous system, echinoderms are capable of complex, coordinated directional behavioral responses...
Despite lacking a brain and having an apparent symmetrically pentaradial nervous system, echinoderms are capable of complex, coordinated directional behavioral responses to different sensory stimuli. However, very little is known about the molecular and cellular mechanisms underlying these behaviors. In many animals, dopaminergic systems play key roles in motivating and coordinating behavior, and although the dopamine receptor antagonist haloperidol has been shown to inhibit the righting response of the sea urchin Strongylocentrotus purpuratus, it is not known whether this is specific to this behavior, in this species, or whether dopaminergic systems are needed in general for echinoderm behaviors. We found that haloperidol inhibited multiple different behavioral responses in three different echinoderm species. Haloperidol inhibited the righting response of the sea urchin Lytechinus variegatus and of the sea star Luidia clathrata. It additionally inhibited the lantern reflex of S. purpuratus, the shell covering response of L. variegatus and the immersion response of L. variegatus, but not S. purpuratus or L. clathrata. Our results suggest that dopamine is needed for the neural processing and coordination of multiple different behavioral responses in a variety of different echinoderm species.
Topics: Animals; Haloperidol; Dopamine Antagonists; Starfish; Sea Urchins
PubMed: 37578035
DOI: 10.1242/jeb.245752 -
Expert Opinion on Investigational Drugs Jun 2017Schizophrenia is a debilitating illness with a chronic impact on social function and daily living. Although various antipsychotics are available, there are still many... (Review)
Review
Schizophrenia is a debilitating illness with a chronic impact on social function and daily living. Although various antipsychotics are available, there are still many challenges and unmet needs. Thus, many compounds with diverse mechanisms have been investigated, but all approved antipsychotics still require interactions with dopamine D receptors. Areas covered: We searched for investigational drugs using the key words 'dopamine' and 'schizophrenia' in American and European clinical trial registers (clinicaltrials.gov; clinicaltrialsregister.eu). Published articles were searched in PubMed, Embase, Medline, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science and the Cochrane Central Register of Controlled Trials Library. Expert opinion: The prospect of developing a dopamine antagonist is hopeful. Brexpiprazole and cariprazine, which were agents listed as 'investigational dopamine antagonists,' just received FDA approval. Novel agents such as BL 1020, ITI-007, and JNJ-37822681 have solid published data available, and agents such as L-THP, Lu AF35700, S33138, and SB-773812 are under vigorous investigation. However, the expected benefits of the newly developed antagonists may not be great because they offer little enhanced efficacy for negative symptoms, cognition and functional outcomes.
Topics: Animals; Antipsychotic Agents; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Drug Design; Drugs, Investigational; Humans; Receptors, Dopamine D2; Schizophrenia
PubMed: 28443355
DOI: 10.1080/13543784.2017.1323870 -
Trends in Pharmacological Sciences Jun 1997The discovery of a novel high-affinity and selective dopamine D4 receptor antagonist, L-745,870, and the results of clinical trials with this compound are reviewed.... (Review)
Review
The discovery of a novel high-affinity and selective dopamine D4 receptor antagonist, L-745,870, and the results of clinical trials with this compound are reviewed. Despite several lines of evidence which suggest that a selective D4 receptor antagonist may be an effective antipsychotic agent with a lower propensity to induce extrapyramidal side-effects, L-745,870 was ineffective as an antipsychotic in humans.
Topics: Animals; Antipsychotic Agents; Biological Availability; Clinical Trials as Topic; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Humans; Pyridines; Pyrroles; Receptors, Dopamine D4; Rodentia; Schizophrenia
PubMed: 9226994
DOI: 10.1016/s0165-6147(97)01066-3