-
Expert Review of Gastroenterology &... Aug 2019: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause... (Review)
Review
: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause of gastroparesis. Management of diabetic gastroparesis involves lifestyle modifications, glycemic control, pharmacological drugs, and for refractory cases surgical treatments. Metoclopramide remains the only drug approved by the Food and Drug Administration for diabetic gastroparesis. The aim of this article is to provide a concise review of the pharmacology, clinical efficacy and tolerability of metoclopramide. : We searched PubMed using the key words 'metoclopramide', 'diabetic gastroparesis', and 'gastric emptying'. The relevant articles and their bibliography were reviewed. Metoclopramide acts on several different receptors; primarily as a dopamine receptor antagonist, both peripherally improving gastric emptying, and centrally resulting in an anti-emetic effect. Metoclopramide side effects, mostly related to its ability to cross the blood-brain barrier, include drowsiness, restlessness, hyperprolactinemia, and tardive dyskinesia (TD), a movement disorder that may be irreversible. : Metoclopramide carries a black box warning for use >12 weeks due to the risk of TD. However, gastroparesis patients experience chronic symptoms often requiring prolonged treatments. Physicians and patients look forward to FDA approval of new agents for gastroparesis with better efficacy and safety profile.
Topics: Diabetes Complications; Dopamine D2 Receptor Antagonists; Gastric Emptying; Gastroparesis; Humans; Metoclopramide; Treatment Outcome; Upper Gastrointestinal Tract
PubMed: 31314613
DOI: 10.1080/17474124.2019.1645594 -
Molecular Pharmaceutics Jun 2020Interaction with the dopaminergic system in the central nervous system is either therapeutically intended or it is a side effect. In both cases, dopamine-receptor...
Interaction with the dopaminergic system in the central nervous system is either therapeutically intended or it is a side effect. In both cases, dopamine-receptor agonists (DRA) like the ergoline derivative bromocriptine and dopamine-receptor antagonists (DRAn) like metoclopramide have to cross the blood-brain barrier (BBB). The organic anion transporting polypeptides (OATP) 1A2 and 2B1 are cellular uptake carriers for a variety of endogenous and xenobiotic compounds. As both transporters are expressed in endothelial cells of the BBB, the aim of the present study was to determine whether the DRA bromocriptine, cabergoline, and pergolide and the DRAn metoclopramide and domperidone are interacting with OATP1A2 and 2B1 and could therefore be candidate genes modifying wanted and unwanted effects of these drugs. Localization of both transporters in the brain was confirmed using LC-MS/MS and immunofluorescence stainings. For the functional studies, MDCKII cells stably expressing OATP1A2 or 2B1 were used. Initial interaction studies with the well-characterized transporter substrate estrone 3-sulfate revealed that all tested compounds except pergolide inhibit the transport function of both proteins with the most potent effect for bromocriptine (IC = 2.2 μM (OATP1A2) and IC = 2.5 μM (OATP2B1)). Further studies using the indirect competitive counterflow method identified bromocriptine, cabergoline, and domperidone as substrates of both transporters, whereas metoclopramide was only transported by OATP1A2. These findings were verified for domperidone by direct measurements using its tritium-labeled form as a tracer. Moreover, the transporter-mediated uptake of this compound was sensitive to the OATP1A2 and OATP2B1 inhibitor naringin. In conclusion, this study suggests that OATP1A2 and 2B1 may play a role in the uptake of DR agonists and antagonists into the brain.
Topics: Animals; Brain; Bromocriptine; Cell Line; Dogs; Domperidone; Dopamine; Dopamine Agonists; Dopamine Antagonists; Humans; Organic Anion Transporters; Pituitary Gland, Anterior; Tandem Mass Spectrometry
PubMed: 32343897
DOI: 10.1021/acs.molpharmaceut.0c00159 -
Neurologic Clinics Nov 2019Diagnostic testing is of limited value among patients with migraine who present to an emergency department. Various nonopioid, disease-specific treatments are available... (Review)
Review
Diagnostic testing is of limited value among patients with migraine who present to an emergency department. Various nonopioid, disease-specific treatments are available for patients who present to an emergency department with migraine headache and associated features. Emergency physicians should recognize that the acute migraine presentation is part of an underlying disorder; care should be geared to the underlying headache disorder in addition to the acute attack.
Topics: Analgesics, Opioid; Dopamine Antagonists; Emergency Medical Services; Emergency Service, Hospital; Humans; Migraine Disorders; Nerve Block
PubMed: 31563230
DOI: 10.1016/j.ncl.2019.07.005 -
Drugs Feb 2021Amisulpride intravenous (IV) injection (Barhemsys; hereafter referred to as IV amisulpride), a selective dopamine receptor antagonist, is approved in the USA as a single... (Review)
Review
Amisulpride intravenous (IV) injection (Barhemsys; hereafter referred to as IV amisulpride), a selective dopamine receptor antagonist, is approved in the USA as a single IV infusion for the prevention and treatment of post-operative nausea and vomiting (PONV) in adults. Results from placebo-controlled phase III trials showed that IV amisulpride is efficacious both in the prevention of PONV (used either alone or in combination with an antiemetic of a different class) and in the treatment of PONV (irrespective of prior antiemetic prophylaxis status). When administered as a single IV infusion, amisulpride had a tolerability profile that was generally similar to that of placebo, with no significant safety concerns identified. Thus, IV amisulpride is a useful additional option in the prevention and treatment of PONV in adults, particularly for patients who have failed previous antiemetic prophylaxis and for whom effective treatment options may be limited.
Topics: Amisulpride; Dopamine Antagonists; Humans; Injections, Intravenous; Postoperative Nausea and Vomiting; Vomiting
PubMed: 33656662
DOI: 10.1007/s40265-020-01462-1 -
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 -
ACS Chemical Neuroscience Sep 2023This study aimed to investigate the changes in retinal neurotransmitters and the role of the dopamine D2 receptor (D2R) pathway in regulating the myopic refractive...
This study aimed to investigate the changes in retinal neurotransmitters and the role of the dopamine D2 receptor (D2R) pathway in regulating the myopic refractive state. Tricolor guinea pigs were randomly divided into two groups: the normal control group (NC) and the form-deprivation myopia group (FDM). Animals in the FDM group had their right eye covered with a balloon for 4 weeks. These two groups were further divided into two subgroups based on intravitreal injection with D2R antagonist sulpiride once a week for 3 weeks (NC, NC-Sul, FDM, and FDM-Sul groups). Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used to quantitatively detect the changes in 17 retinal neurotransmitters. Compared to the NC group, the concentrations of dopamine (DA) and γ-aminobutyric acid (GABA) decreased, while those of glutamate (Glu), 3-methoxytyramine (3-MT), and glycine increased, accompanied by an increase in myopic refraction and axial length (AL) in the FDM group. In the FDM-Sul group, glycine and DA levels were upregulated, whereas 3-MT and Glu levels were downregulated, accompanied by a decrease in myopic refraction and AL. The ratio of Glu to GABA (RGG) represents the balance between excitatory and inhibitory neurotransmitters. Notably, RGG changes occurred with corresponding AL changes, which increased in the FDM group and decreased in the FDM-Sul group. Decreased retinal DA concentration, with an increase in Glu, may be involved in the myopia progression. D2R antagonists might effectively slow myopia progression by increasing retinal DA, regulating Glu concentration to match GABA, and maintaining the balance between excitatory and inhibitory neurotransmitters.
Topics: Guinea Pigs; Animals; Dopamine D2 Receptor Antagonists; Myopia; Glutamic Acid; Glycine; gamma-Aminobutyric Acid
PubMed: 37647579
DOI: 10.1021/acschemneuro.3c00099 -
Scientific Reports Jan 2022The posterior pallial amygdala (PoA) is located on the basolateral caudal telencephalon, including the basal division of PoA (PoAb) and the compact division of PoA...
The posterior pallial amygdala (PoA) is located on the basolateral caudal telencephalon, including the basal division of PoA (PoAb) and the compact division of PoA (PoAc). PoA plays a vital role in emotion regulation and is considered a part of the amygdala in birds. However, the regulatory functions responsible for motor behaviors and emotions between PoAb and PoAc are poorly understood. Therefore, we studied the structure and function of PoA by tract-tracing methods, constant current electrical stimulation, and different dopamine receptor drug injections in pigeons (Columba livia domestica). PoAb connects reciprocally with two nuclear groups in the cerebrum: 1) a continuum comprising the temporo-parieto-occipitalis, corticoidea dorsolateralis, hippocampus, and parahippocampalis areas and 2) rostral areas of the hemisphere, including the nucleus septalis lateralis and nucleus taeniae amygdalae. Extratelencephalic projections of PoAb terminate in the lateral hypothalamic nucleus and are scattered in many limbic midbrain regions. PoAb and PoAc mainly mediated the turning movement. In the 'open-field' test, D1 agonist and D2 antagonist could significantly reduce the latency period for entering into the central area and increase the residence time in the central area, whereas D1 antagonist and D2 agonist had the opposite effect. PoAb and PoAc are important brain areas that mediate turning behavior.
Topics: Amygdala; Animals; Behavior, Animal; Columbidae; Dopamine; Dopamine Agonists; Dopamine Antagonists; Dopaminergic Neurons; Electric Stimulation; Female; Male; Motor Activity; Neuroanatomical Tract-Tracing Techniques; Open Field Test; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 35013368
DOI: 10.1038/s41598-021-03876-7 -
American Journal of Therapeutics 2019
Topics: Bipolar Disorder; Delirium; Dopamine D2 Receptor Antagonists; Humans; Lurasidone Hydrochloride; Male; Middle Aged; Psychiatric Status Rating Scales; Serotonin 5-HT2 Receptor Antagonists
PubMed: 30839323
DOI: 10.1097/MJT.0000000000000959 -
Best Practice & Research. Clinical... Dec 2020Intraoperative and postoperative nausea and vomiting (IONV and PONV) afflict up to 80% of parturients undergoing cesarean delivery with neuraxial anesthesia. Preventing... (Review)
Review
Intraoperative and postoperative nausea and vomiting (IONV and PONV) afflict up to 80% of parturients undergoing cesarean delivery with neuraxial anesthesia. Preventing nausea and emesis is a top priority for women undergoing cesarean delivery and is included in the quality of recovery measures and enhanced recovery after cesarean delivery protocols. The majority of known perioperative emetic triggers can be avoided or mitigated by optimizing anesthetic and surgical management. IONV may arise from spinal anesthesia-induced hypotension, intraoperative pain, and medications such as uterotonics and antibiotics. Furthermore, uterine exteriorization and peritoneal irrigation increase IONV risk. Conversely, preventing PONV mainly focuses on optimizing analgesia through an opioid-sparing, multimodal strategy. In addition, combination prophylactic antiemetic therapy should be instituted in this high-risk population to further reduce the risk of IONV and PONV.
Topics: Anesthesia, Obstetrical; Antiemetics; Cesarean Section; Dopamine Antagonists; Female; Humans; Injections, Spinal; Intraoperative Complications; Postoperative Nausea and Vomiting; Pregnancy; Serotonin 5-HT3 Receptor Antagonists
PubMed: 33288123
DOI: 10.1016/j.bpa.2020.04.012 -
Proteomics Sep 2023The retinal pigment epithelial (RPE)/choroid complex regulates myopia development, but the precise pathogenesis of myopia remains unclear. We aimed to investigate the...
The retinal pigment epithelial (RPE)/choroid complex regulates myopia development, but the precise pathogenesis of myopia remains unclear. We aimed to investigate the changes in RPE/choroid complex metabolism in a form deprivation myopia model after dopamine D2 receptor (D2R) modulation. Guinea pigs were randomly divided into normal (NC), form deprivation myopia (FDM), and FDM treated with dopamine D2R antagonist groups. Differential metabolites were screened using SIMCA-P software and MetaboAnalyst metabolomics analysis tool. Functions of differential metabolites were analyzed using KEGG enrichment pathways. Relative to the NC group, 38 differential metabolites were identified, comprising 29 increased metabolites (including nicotinic acid, cytosine, and glutamate) and 9 decreased metabolites, of which proline exhibited the largest decrease. Pathway analysis revealed regulation of arginine/proline and aspartate/glutamate metabolism. Intravitreal D2R antagonist injection increased proline concentrations and activated arginine/proline and purine metabolism pathways. In sum, D2R antagonists alleviated the myopia trend of refractive biological parameters in form deprivation myopic guinea pigs, suggesting the involvement of dopamine D2R signaling in myopia pathogenesis. The RPE/choroid may provide glutamate to the retina by activating proline metabolism via metabolic coupling with the retina. Dopamine D2R antagonism may modulate proline/arginine metabolic pathways in the RPE/choroid and regulate metabolism, information presentation, and myopia.
Topics: Guinea Pigs; Animals; Dopamine; Dopamine D2 Receptor Antagonists; Retina; Myopia; Choroid; Glutamates; Disease Models, Animal
PubMed: 37491763
DOI: 10.1002/pmic.202200325