Displaying publications 41 - 60 of 102 in total

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  1. Normobaric hyperoxia treatment prevents early alteration in dopamine level in mice striatum after fluid percussion injury: a biochemical approach
    Muthuraju S, Islam MR, Pati S, Jaafar H, Abdullah JM, Yusoff KM
    Int J Neurosci, 2015;125(9):686-92.
    PMID: 25180987 DOI: 10.3109/00207454.2014.961065
    Dopamine (DA) is one of the key neurotransmitters in the striatum, which is functionally important for a variety of cognitive and motor behaviours. It is known that the striatum is vulnerable to damage from traumatic brain injury (TBI). However, a therapeutic approach has not yet been established to treat TBI. Hence, the present work aimed to evaluate the ability of Normobaric hyperoxia treatment (NBOT) to recover dopaminergic neurons following a fluid percussion injury (FPI) as a TBI experimental animal model. To examine this, mice were divided into four groups: (i) Control, (ii) Sham, (iii) FPI and (iv) FPI+NBOT. Mice were anesthetized and surgically prepared for FPI in the striatum and immediate exposure to NBOT at various time points (3, 6, 12 and 24 h). Dopamine levels were then estimated post injury by utilizing a commercially available ELISA method specific to DA. We found that DA levels were significantly reduced at 3 h, but there was no reduction at 6, 12 and 24 h in FPI groups when compared to the control and sham groups. Subjects receiving NBOT showed consistent increased DA levels at each time point when compared with Sham and FPI groups. These results suggest that FPI may alter DA levels at the early post-TBI stages but not in later stages. While DA levels increased in 6, 12 and 24 h in the FPI groups, NBOT could be used to accelerate the prevention of early dopaminergic neuronal damage following FPI injury and improve DA levels consistently.
    Matched MeSH terms: Dopamine/metabolism*; Dopaminergic Neurons/metabolism*
  2. Fulltext No evidence for association between DRD3 and COMT with schizophrenia in a Malay population
    Tee SF, Tang PY, Loh HC
    Genet. Mol. Res., 2011;10(3):1850-5.
    PMID: 21948748 DOI: 10.4238/vol10-3gmr1237
    Molecular components of the dopamine D3 receptor (DRD3) may play an important role in the pathophysiology of schizophrenia. Previous studies have demonstrated an association between DRD3 Ser9Gly and cathechol-o-methyltransferase (COMT, SNP = rs165656) polymorphisms and schizophrenia but the results were inconclusive. We investigated this apparent association between Ser9Gly (A/G) polymorphism and an intronic SNP (dbSNP or rs165656) in 261 Malay patients diagnosed with schizophrenia and 216 controls, using PCR-RFLP. The genotype distribution of the polymorphism DRD3 Ser9Gly was in Hardy-Weinberg equilibrium (HWE) for patients (P = 0.1251) and out of HWE for controls (P = 0.0137). However, both healthy controls and schizophrenia patients were out of HWE for the polymorphism COMT rs165656. Based on allele and genotype frequencies in both groups, we found no significant association of DRD3 Ser9Gly polymorphisms and COMT (rs165656) with schizophrenia in Malays. Further studies should examine the association between other dopamine-related genes and the behavioral phenotypes of schizophrenia.
    Matched MeSH terms: Receptors, Dopamine D3/genetics*
  3. Tridimensional personalities and polymorphism of dopamine D2 receptor among heroin addicts
    Teh LK, Izuddin AF, M H FH, Zakaria ZA, Salleh MZ
    Biol Res Nurs, 2012 Apr;14(2):188-96.
    PMID: 21613340 DOI: 10.1177/1099800411405030
    Drug addiction is a multifactorial disorder. Researchers have posited that an individual's inherited behavioral propensity or temperament contributes to the disorder by shaping a personality strongly linked with the risk of drug abuse. Further, they hypothesize that the polymorphism of dopamine D2 receptor increases the susceptibility to and severity of addiction. We, therefore, investigated possible associations between dopamine D2 receptor (DRD2) and personality traits among intravenous heroin addicts.
    Matched MeSH terms: Receptors, Dopamine D2/genetics*
  4. Influence of DRD2 polymorphisms on the clinical outcomes of patients with schizophrenia
    Zahari Z, Teh LK, Ismail R, Razali SM
    Psychiatr Genet, 2011 Aug;21(4):183-9.
    PMID: 21206399 DOI: 10.1097/YPG.0b013e3283437250
    Variations in the gene for dopamine D2 receptor (DRD2) might have an influence on the outcome of antipsychotic treatment in schizophrenia. The objective of this study was to investigate the influence of DRD2 polymorphisms on treatment outcomes in patients with schizophrenia.
    Matched MeSH terms: Receptors, Dopamine D2/genetics*
  5. Fabrication of CoTiO3-TiO2 composite films from a heterobimetallic single source precursor for electrochemical sensing of dopamine
    Ehsan MA, Naeem R, Khaledi H, Sohail M, Hakeem Saeed A, Mazhar M
    Dalton Trans, 2016 Jun 21;45(25):10222-32.
    PMID: 27230711 DOI: 10.1039/c6dt01016d
    Cobalt titanate-titania composite oxide films have been grown on FTO-coated glass substrates using a single-source heterometallic complex [Co2Ti4(μ-O)6(TFA)8(THF)6]·THF () which was obtained in quantitative yield from the reaction of diacetatocobalt(ii) tetrahydrate, tetraisopropoxytitanium(iv), and trifluoroacetic acid from a tetrahydrofuran solution. Physicochemical investigations of complex have been carried out by melting point, FT-IR, thermogravimetric and single-crystal X-ray diffraction analyses. CoTiO3-TiO2 films composed of spherical objects of various sizes have been grown from by aerosol-assisted chemical vapor deposition at different temperatures of 500, 550 and 600 °C. Thin films characterized by XRD, Raman and X-ray photoelectron spectroscopy, scanning electron microscopy, energy-dispersive X-ray analysis have been explored for electrochemical detection of dopamine (DA). The cyclic voltammetry with the CoTiO3-TiO2 electrode showed a DA oxidation peak at +0.215 V while linear sweep voltammetry displayed a detection limit (LoD) of 0.083 μM and a linear concentration range of 20-300 μM for DA. Thus, the CoTiO3-TiO2 electrode is a potential candidate for the sensitive and selective detection of DA.
    Matched MeSH terms: Dopamine/analysis*
  6. The Functional Significance of Endocrine-immune Interactions in Health and Disease
    Muthusami S, Vidya B, Shankar EM, Vadivelu J, Ramachandran I, Stanley JA, et al.
    Curr Protein Pept Sci, 2020;21(1):52-65.
    PMID: 31702489 DOI: 10.2174/1389203720666191106113435
    Hormones are known to influence various body systems that include skeletal, cardiac, digestive, excretory, and immune systems. Emerging investigations suggest the key role played by secretions of endocrine glands in immune cell differentiation, proliferation, activation, and memory attributes of the immune system. The link between steroid hormones such as glucocorticoids and inflammation is widely known. However, the role of peptide hormones and amino acid derivatives such as growth and thyroid hormones, prolactin, dopamine, and thymopoietin in regulating the functioning of the immune system remains unclear. Here, we reviewed the findings pertinent to the functional role of hormone-immune interactions in health and disease and proposed perspective directions for translational research in the field.
    Matched MeSH terms: Dopamine/genetics; Dopamine/immunology; Dopamine/metabolism; Receptors, Dopamine/genetics; Receptors, Dopamine/immunology; Receptors, Dopamine/metabolism
  7. Fulltext An inhibited dopamine synthesizing cell model of AADC deficiency
    Melati Khalid, Mohamad Aris Mohd Moklas
    Life Sciences, Medicine and Biomedicine, 2019;3(2):1-7.
    MyJurnal
    Aromatic L-amino acid decarboxylase deficiency (AADC) is a rare autosomal recessive pediatric neurotransmitter disease. To date it remains poorly understood mainly due to an absence of a disease model. The dopaminergic neuroblastoma cell SH-SY5Y was chosen to develop our AADC deficiency model. These cells are not native dopamine synthesizers. Objective: To develop a dopamine-producing cellular model of AADC deficiency using SH-SY5Y neuroblastoma cells. Methods: Dopamine pathway proteins were identified with Western Blotting. Dopaminergic differentiation was attempted using all-trans retinoic acid (ATRA) with dopamine detection via HPLC-ECD post alumina extraction. Treatment with L-DOPA provided SH-SY5Y with excess precursor. RT-PCR was used to determine the expression of markers of mature neurons. Results: Western Blot screening identified AADC, dopamine β-hydroxylase and tyrosine hyrdoxylase proteins, indicative of a dopaminergic pathway. ATRA was unsuccessful in producing dopamine from the cells. L-DOPA treatment however, generated dopamine first visible as a HPLC-ECD peak 30 minutes post-incubation. Prior to this, SH-SY5Y dopamine synthesis from L-DOPA has never been documented. This de novo synthesis is then inhibited using benserazide to form our AADC deficiency cell model. RT-PCR showed that SH-SY5Y cells express markers of mature neurons in its ‘native’ state and is not affected by L-DOPA and benserazide treatment. This cell model will potentially benefit many areas of AADC deficiency research. Conclusion: SH-SY5Y cells produced HPLC-ECD measureable amounts of dopamine with the addition of L-DOPA. Our model of AADC deficiency is generated by quelling the dopamine production with Benserazide.
    Matched MeSH terms: Dopamine; Dopamine beta-Hydroxylase; Dopaminergic Neurons
  8. The evolutionary strata of DARPP-32 tail implicates hierarchical functional expansion in higher vertebrates
    Ung CY, Teoh TC
    J Biosci, 2014 Jun;39(3):493-504.
    PMID: 24845512
    DARPP-32 (dopamine and adenosine 3', 5'-monophosphate-regulated phosphoprotein of 32 kDa), which belongs to PPP1R1 gene family, is known to act as an important integrator in dopamine-mediated neurotransmission via the inhibition of protein phosphatase-1 (PP1). Besides its neuronal roles, this protein also behaves as a key player in pathological and pharmacological aspects. Use of bioinformatics and phylogenetics approaches to further characterize the molecular features of DARPP-32 can guide future works. Predicted phosphorylation sites on DARPP-32 show conservation across vertebrates. Phylogenetics analysis indicates evolutionary strata of phosphorylation site acquisition at the C-terminus, suggesting functional expansion of DARPP-32, where more diverse signalling cues may involve in regulating DARPP-32 in inhibiting PP1 activity. Moreover, both phylogenetics and synteny analyses suggest de novo origination of PPP1R1 gene family via chromosomal rearrangement and exonization.
    Matched MeSH terms: Dopamine and cAMP-Regulated Phosphoprotein 32/chemistry*
  9. Natural Products Combating Neurodegeneration: Parkinson's Disease
    Solayman M, Islam MA, Alam F, Khalil MI, Kamal MA, Gan SH
    Curr Drug Metab, 2017;18(1):50-61.
    PMID: 27396919 DOI: 10.2174/1389200217666160709204826
    Parkinson's disease (PD) is characterized by neurodegeneration and a progressive functional impairment of the midbrain nigral dopaminergic neurons. The cause remains unknown; however, several pathological processes and central factors, such as protein aggregation, mitochondrial dysfunction, iron accumulation, neuroinflammation and oxidative stress, have been reported. The current treatment method primarily targets symptoms by using anti-Parkinson drugs such as levodopa, carbidopa, dopamine (DA) agonists, monoamine oxidase type B inhibitors and anticholinergics to replace DA. When drug therapy is not satisfactory, surgical treatments are recommended. Unfortunately, the existing conventional strategies that target PD are associated with numerous side effects and possess an economic burden. Therefore, novel therapeutic approaches that regulate the pathways leading to neuronal death and dysfunction are necessary. For many years, nature has provided the primary resource for the discovery of potential therapeutic agents. Remarkably, many natural products from medicinal plants, fruits and vegetables have been demonstrated to be efficacious anti-Parkinson agents. These products possess neuroprotective properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding iron accumulation, protein misfolding and the maintenance of proteasomal degradation, as well as mitochondrial homeostasis. The aim of this review is to report the available anti-Parkinson agents based on natural products and delineate their therapeutic actions, which act on various pathways. Overall, this review emphasizes the types of natural products that are potential future resources in the treatment of PD as novel regimens or supplementary agents.
    Matched MeSH terms: Dopamine; Dopamine Agonists; Dopaminergic Neurons
  10. Simultaneous determination of ascorbic acid, dopamine and uric acid by a novel electrochemical sensor based on N2/Ar RF plasma assisted graphene nanosheets/graphene nanoribbons
    Jothi L, Neogi S, Jaganathan SK, Nageswaran G
    Biosens Bioelectron, 2018 May 15;105:236-242.
    PMID: 29412948 DOI: 10.1016/j.bios.2018.01.040
    A novel nitrogen/argon (N2/Ar) radio frequency (RF) plasma functionalized graphene nanosheet/graphene nanoribbon (GS/GNR) hybrid material (N2/Ar/GS/GNR) was developed for simultaneous determination of ascorbic acid (AA), dopamine (DA) and uric acid (UA). Various nitrogen mites introduced into GS/GNR hybrid structure was evidenced by a detailed microscopic, spectroscopic and surface area analysis. Owing to the unique structure and properties originating from the enhanced surface area, nitrogen functional groups and defects introduced on both the basal and edges, N2/Ar/GS/GNR/GCE showed high electrocatalytic activity for the electrochemical oxidations of AA, DA, and UA with the respective lowest detection limits of 5.3, 2.5 and 5.7 nM and peak-to-peak separation potential (ΔEP) (vs Ag/AgCl) in DPV of 220, 152 and 372 mV for AA/DA, DA/UA and AA/UA respectively. Moreover, the selectivity, stability, repeatability and excellent performance in real time application of the fabricated N2/Ar/GS/GNR/GCE electrode suggests that it can be considered as a potential electrode material for simultaneous detection of AA, DA, and UA.
    Matched MeSH terms: Dopamine/blood*
  11. The Role of Monoamine Oxidase B Inhibitors in the Treatment of Parkinson's Disease - An Update
    Chew ZX, Lim CL, Ng KY, Chye SM, Ling APK, Koh RY
    CNS Neurol Disord Drug Targets, 2023;22(3):329-352.
    PMID: 34970960 DOI: 10.2174/1871527321666211231100255
    Parkinson's disease (PD) is a progressive neurodegenerative disease characterised by reduced dopamine levels in the substantial nigra. This may lead to typical motor features such as bradykinesia, resting tremors and rigid muscles, as well as non-motor symptoms such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunction, and sensory disturbances. Inhibitors of monoamine oxidase B (MAO-B) are used to alleviate symptoms by reducing monoamine oxidase-catalysed degradation of dopamine; hence, preserving functional levels of dopamine. The very first MAO-B inhibitor used therapeutically was selegiline, followed by rasagiline, its indane derivative which has superior efficacy and selectivity. Both inhibitors can be used as monotherapy or in combination with other anti- Parkinson drugs. Safinamide, a reversible MAO-B inhibitor that utilises both dopaminergic and non-dopaminergic mechanisms, was recently approved by the European Medicines Agency (EMA) (2015) and U.S. FDA (2017) as an add-on therapy for patients with mid- or late-stage Parkinson's disease. Furthermore, MAO-B inhibitors were found to be associated with potential neuroprotective and disease modifying effects. However, evidence of their efficacy and role in PD models is scarce and warrants further investigation.
    Matched MeSH terms: Dopamine; Dopamine Agents
  12. The effects of metallothionein in paraquat-induced Parkinson disease model of zebrafish
    Mohamad Najib NH, Yahaya MF, Das S, Teoh SL
    Int J Neurosci, 2023 Dec;133(8):822-833.
    PMID: 34623211 DOI: 10.1080/00207454.2021.1990916
    INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Metallothionein has been shown to act as a neuroprotectant in various brain injury. Thus, this study aims to identify the effects of full-length human metallothionein 2 peptide (hMT2) in paraquat-induced brain injury in the zebrafish.

    METHODOLOGY: A total of 80 adult zebrafish were divided into 4 groups namely control, paraquat-treated, pre-hMT2-treated, and post-hMT2-treated groups. Fish were treated with paraquat intraperitoneally every 3 days for 15 days. hMT2 were injected intracranially on day 0 (pre-treated group) and day 16 (post-treated group). Fish were sacrificed on day 22 and the brains were collected for qPCR, ELISA and immunohistochemistry analysis.

    RESULTS: qPCR analysis showed that paraquat treatment down-regulated the expression of genes related to dopamine activity and biosynthesis (dat and th1) and neuroprotective agent (bdnf). Paraquat treatment also up-regulated the expression of the mt2, smtb and proinflammatory genes (il-1α, il-1β, tnf-α and cox-2). hMT2 treatment was able to reverse the effects of paraquat. Lipid peroxidation decreased in the paraquat and pre-hMT2-treated groups. However, lipid peroxidation increased in the post-hMT2-treated group. Paraquat treatment also led to a reduction of dopaminergic neurons while their numbers showed an increase following hMT2 treatment.

    CONCLUSION: Paraquat has been identified as one of the pesticides that can cause the death of dopaminergic neurons and affect dopamine biosynthesis. Treatment with exogenous hMT2 could reverse the effects of paraquat in the zebrafish brain.

    Matched MeSH terms: Dopamine/metabolism; Dopaminergic Neurons/metabolism
  13. Fulltext Recent Advances in Electrochemical and Optical Sensing of Dopamine
    Kamal Eddin FB, Wing Fen Y
    Sensors (Basel), 2020 Feb 14;20(4).
    PMID: 32075167 DOI: 10.3390/s20041039
    Nowadays, several neurological disorders and neurocrine tumours are associated with dopamine (DA) concentrations in various biological fluids. Highly accurate and ultrasensitive detection of DA levels in different biological samples in real-time can change and improve the quality of a patient's life in addition to reducing the treatment cost. Therefore, the design and development of diagnostic tool for in vivo and in vitro monitoring of DA is of considerable clinical and pharmacological importance. In recent decades, a large number of techniques have been established for DA detection, including chromatography coupled to mass spectrometry, spectroscopic approaches, and electrochemical (EC) methods. These methods are effective, but most of them still have some drawbacks such as consuming time, effort, and money. Added to that, sometimes they need complex procedures to obtain good sensitivity and suffer from low selectivity due to interference from other biological species such as uric acid (UA) and ascorbic acid (AA). Advanced materials can offer remarkable opportunities to overcome drawbacks in conventional DA sensors. This review aims to explain challenges related to DA detection using different techniques, and to summarize and highlight recent advancements in materials used and approaches applied for several sensor surface modification for the monitoring of DA. Also, it focuses on the analytical features of the EC and optical-based sensing techniques available.
    Matched MeSH terms: Dopamine/analysis*
  14. Fulltext Highly exposed {001} facets of titanium dioxide modified with reduced graphene oxide for dopamine sensing
    How GT, Pandikumar A, Ming HN, Ngee LH
    Sci Rep, 2014;4:5044.
    PMID: 24853929 DOI: 10.1038/srep05044
    Titanium dioxide (TiO2) with highly exposed {001} facets was synthesized through a facile solvo-thermal method and its surface was decorated by using reduced graphene oxide (rGO) sheets. The morphology and chemical composition of the prepared rGO/TiO2 {001} nanocomposite were examined by using suitable characterization techniques. The rGO/TiO2 {001} nanocomposite was used to modify glassy carbon electrode (GCE), which showed higher electrocatalytic activity towards the oxidation of dopamine (DA) and ascorbic acid (AA), when compared to unmodified GCE. The differential pulse voltammetric studies revealed good sensitivity and selectivity nature of the rGO/TiO2 {001} nanocomposite modified GCE for the detection of DA in the presence of AA. The modified GCE exhibited a low electrochemical detection limit of 6 μM over the linear range of 2-60 μM. Overall, this work provides a simple platform for the development of GCE modified with rGO/TiO2 {001} nanocomposite with highly exposed {001} facets for potential electrochemical sensing applications.
    Matched MeSH terms: Dopamine/analysis*
  15. Fulltext Discovery of indolylpiperazinylpyrimidines with dual-target profiles at adenosine A2A and dopamine D2 receptors for Parkinson's disease treatment
    Shao YM, Ma X, Paira P, Tan A, Herr DR, Lim KL, et al.
    PLoS One, 2018;13(1):e0188212.
    PMID: 29304113 DOI: 10.1371/journal.pone.0188212
    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7-11.2 μM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5-40.2 μM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 μM), hepatotoxicity (up to 30 μM) or cardiotoxicity (up to 30 μM).
    Matched MeSH terms: Receptors, Dopamine D2/metabolism*; Receptors, Dopamine D2/agonists*; Dopamine Agonists/pharmacokinetics; Dopamine Agonists/pharmacology*; Dopamine Agonists/chemistry
  16. Effects of age on the glucoregulatory response following acute glucoprivation induced by 2-deoxyglucose (2DG) in the adrenal medulla of Sprague Dawley rats
    Muda NA, Ramlan H, Damanhuri HA
    Neuro Endocrinol. Lett., 2017 Jul;38(3):224-235.
    PMID: 28759191
    OBJECTIVES: Impairment in glucose homeostasis is one of the factors that may alter the feeding drive, hunger and satiety signals, which essential to maintain a sufficient level of energy for daily activities especially among the elderly. Adrenal medulla is one of the important organs that involves in glucose homeostasis through secretion of catecholamines. The catecholamines biosynthesis pathway utilizes various enzymes and protein kinases. The aims of this study are to investigate the effects of age on the biosynthetic pathway of catecholamines in adrenal medulla by determining the level of blood glucose and blood catecholamines, the gene and protein expression of biosynthetic catecholamine enzymes (TH, DBH and PNMT) as well as protein kinase substrates that involved in the phosphorylation of TH in 2DG-induced rats.

    METHODS: Adrenal medulla from male Sprague Dawley rats at the age of 3-months (n=12) and 24-months (n=12) were further divided into two groups: 1) treatment group with 2DG to create glucoprivation condition and 2) the vehicle group which received normal saline as control.

    RESULTS: The results showed that the level of glucose, adrenaline and noradrenaline were increased in response to acute glucoprivation conditions in both young and old rats. No age-related differences were found in the basal gene expression of the enzymes that involved in the catecholamines biosynthesis pathway. Interestingly the expressions of TH and DBH protein as well as the level of TH phosphorylation at Ser40, PKA, PKC and ERK1/2 substrates were higher in basal condition of the aged rats. However, contradicted findings were obtained in glucoprivic condition, which the protein expressions of DBH, pERK1/2 and substrates for pPKC were increased in young rats. Only substrate for pCDK was highly expressed in the old rats in the glucoprivic condition, while pPKC and pERK1/2 were decreased significantly. The results demonstrate that adrenal medulla of young and old rats are responsive to glucose deficit and capable to restore the blood glucose level by increasing the levels of blood catecholamines.

    CONCLUSION: The present findings also suggest that, at least in rats, aging alters the protein expression of the biosynthetic catecholamine enzymes as well as protein kinase substrates that may attenuate the response to glucoprivation.

    Matched MeSH terms: Dopamine beta-Hydroxylase/genetics; Dopamine beta-Hydroxylase/metabolism
  17. Luteolin, a Potent Human Monoamine Oxidase-A Inhibitor and Dopamine D4 and Vasopressin V1A Receptor Antagonist
    Park SE, Paudel P, Wagle A, Seong SH, Kim HR, Fauzi FM, et al.
    J Agric Food Chem, 2020 Sep 30;68(39):10719-10729.
    PMID: 32869630 DOI: 10.1021/acs.jafc.0c04502
    Luteolin, a flavonoid widely distributed in the plant kingdom, contains two benzene rings and hydroxyl groups, and this structural specificity contributes to its diverse biological activities. However, no previous studies have simultaneously investigated the therapeutic potency of luteolin isolated from a plant as an antipsychotic and antidepressant. Here, luteolin exhibited selective inhibition of hMAO-A (IC50 = 8.57 ± 0.47 μM) over hMAO-B (IC50 > 100 μM). In silico proteochemometric modeling predicted promising targets of luteolin, and verification via cell-based G protein-coupled receptor functional assays showed that luteolin is a selective antagonist of the vasopressin receptor V1AR (IC50 = 19.49 ± 6.32 μM) and the dopamine D4 receptor (IC50 = 39.59 ± 1.46 μM). Molecular docking showed the tight binding of luteolin with a low binding score and the high stability of the luteolin-receptor complex, corroborating its functional effect. Thus, hMAO-A, hD4R, and hV1AR are prime targets of luteolin and potential alternatives for the management of neurodegenerative diseases.
    Matched MeSH terms: Receptors, Dopamine D4
  18. Fulltext Metoclopramide-Induced Acute Dystonic Reactions May Be Associated With the CYP2D6 Poor Metabolizer Status and Pregnancy-Related Hormonal Changes
    Chua EW, Harger SP, Kennedy MA
    Front Pharmacol, 2019;10:931.
    PMID: 31507424 DOI: 10.3389/fphar.2019.00931
    We report two cases of metoclopramide-induced acute dystonia in pregnant women and consider the role of genetic variation in the pathogenesis of the adverse effect. By whole-gene sequencing, we found that both women were CYP2D6 poor metabolizers. We theorize that CYP2D6 governs the risk of metoclopramide-related acute dystonia through its role in the synthesis of serotonin, which inhibits the dopamine tone. The effect of CYP2D6 poor metabolism is exaggerated by rises in the estrogen levels during pregnancy, as the hormone augments dopamine sensitivity. Together, the two factors may create a hyper-dopaminergic state that is easily upset by metoclopramide, resulting in acute dystonia.
    Matched MeSH terms: Dopamine
  19. Fulltext A rare case of Riamet induced prolonged corrected QT interval
    Neesha Sundramoorthy, Khaiteri R., Jer Ming Low, Chan Soon Thim Darren
    Malaysian Journal of Medicine and Health Sciences, 2019;15(106):70-70.
    MyJurnal
    Introduction: Artemether and lumefantrine was registered as Riamet in Switzerland in 1999 and is commonly used in Keningau Hospital for managing uncomplicated malaria. Riamet works at the food vacoule of the malarial parasite, where they interfere with the conversion of heme into haemozoin. Case description: We report a case of Riamet induced prolonged corrected QT interval (QTc) in a 37 year old gentleman admitted for severe malaria (hypotension) with normal QTc of 420msc on presentation. Upon starting Riamet, he developed bradycardia and ECG showed sinus bradycardia with prolonged QTc of 551msec and no arrythmias. Echocardiography showed no structural heart abnormalities. All electrolytes were within normal range. He was monitored in cardiac care unit with decision to complete 6 doses of Riamet. Patient was started on Dopamine infusion which maintained his blood pressure and heart rate within normal range. 5 days post Riamet completion, his heart rate improved and dopamine infusion was tapered off and QTc normalized to 407msc. Discussion: The most common mechanism of drugs causing QT inter-val prolongation is by blocking the human ether-à-go-go related gene (hERG) potassium channel. Blockage of the hEGR channel lengthens ventricular re-polarization and duration of ventricular action potential which is reflected in ECG as prolonged QT interval. In the in-vitro whole cell patch clamp study, lumefantrine and its metabolite desbu-tyl-lumefantrine showed a concentration-dependent inhibition of the hERG current. The period of QTc prolongation was 3.5 to 4 days after the last dose of the standard 6 dose regimen. Conclusion: Riamet induced prolonged QTc is a very rare complication. A baseline electrocardiography is therefore imminent for every patient prior to initiation of this medication to avoid cardiac arrythmias.
    Matched MeSH terms: Dopamine
  20. Fulltext Suppression of Cisplatin-Induced Vomiting byCannabis sativain Pigeons: Neurochemical Evidences
    Ullah I, Subhan F, Alam J, Shahid M, Ayaz M
    Front Pharmacol, 2018;9:231.
    PMID: 29615907 DOI: 10.3389/fphar.2018.00231
    Cannabis sativa
    (CS, familyCannabinaceae) has been reported for its anti-emetic activity against cancer chemotherapy-induced emesis in animal models and in clinics. The current study was designed to investigateCSfor potential effectiveness to attenuate cisplatin-induced vomiting in healthy pigeons and to study the impact on neurotransmitters involved centrally and peripherally in the act of vomiting. High-performance liquid chromatography system coupled with electrochemical detector was used for the quantification of neurotransmitters 5-hydroxytryptamine (5HT), dopamine (DA) and their metabolites; Di-hydroxy Phenyl Acetic acid (Dopac), Homovanillic acid (HVA), and 5-hydroxy indole acetic acid (5HIAA) centrally in specific brain areas (area postrema and brain stem) while, peripherally in small intestine. Cisplatin (7 mg/kg i.v.) induce emesis without lethality across the 24 h observation period.CShexane fraction (CS-HexFr; 10 mg/kg) attenuated cisplatin-induced emesis ∼ 65.85% (P< 0.05); the reference anti-emetic drug, metoclopramide (MCP; 30 mg/kg), produced ∼43.90% reduction (P< 0.05). At acute time point (3rdh), CS-HexFr decreased (P< 0.001) the concentration of 5HT and 5HIAA in the area postrema, brain stem and intestine, while at 18thh (delayed time point) CS-HexFr attenuated (P< 0.001) the upsurge of 5HT caused by cisplatin in the brain stem and intestine and dopamine in the area postrema.CS-HexFr treatment alone did not alter the basal neurotransmitters and their metabolites in the brain areas and intestine except 5HIAA and HVA, which were decreased significantly. In conclusion the anti-emetic effect ofCS-HexFr is mediated by anti-serotonergic and anti-dopaminergic components in a blended manner at the two different time points, i.e., 3rdand 18thh in pigeons.
    Matched MeSH terms: Dopamine
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