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Maturation of the adrenal medulla--IV. Effects of morphine

Anderson TR, Slotkin TA

Biochem Pharmacol, 1975 Aug 15;24(16):1469-74.
PMID: 7
Matched MeSH terms: Dopamine beta-Hydroxylase/metabolism
A Double-Blind Randomized Controlled Trial of High Cutoff Versus Standard Hemofiltration in Critically Ill Patients With Acute Kidney Injury

Atan R, Peck L, Prowle J, Licari E, Eastwood GM, Storr M, et al.

Crit Care Med, 2018 10;46(10):e988-e994.
PMID: 30074491 DOI: 10.1097/CCM.0000000000003350

OBJECTIVES: In critically ill patients with acute kidney injury receiving vasopressors, high cytokine levels may sustain the shock state. High cutoff hemofiltration achieves greater cytokine removal in ex vivo and in animal models and may reduce the duration of shock but may also increase albumin losses.
DESIGN: This was a single-center double-blind randomized controlled trial comparing continuous venovenous hemofiltration-high cutoff to continuous venovenous hemofiltration-standard.
SETTING: Tertiary care hospital in Australia.
PATIENTS: Vasopressor-dependent patients in acute kidney injury who were admitted to the ICU.
INTERVENTIONS: Norepinephrine-free time were calculated in critically ill vasopressor-dependent patients in acute kidney injury, randomized to either continuous venovenous hemofiltration-high cutoff or continuous venovenous hemofiltration-standard.
MEASUREMENT AND MAIN RESULTS: A total of 76 patients were randomized with the following characteristics (continuous venovenous hemofiltration-high cutoff vs continuous venovenous hemofiltration-standard); median age of 65 versus 70 year, percentage of males 47% versus 68%, and median Acute Physiology and Chronic Health Evaluation scores of 25 versus 23.5. The median hours of norepinephrine-free time at day 7 were 32 (0-110.8) for continuous venovenous hemofiltration-high cutoff and 56 hours (0-109.3 hr) (p = 0.520) for continuous venovenous hemofiltration-standard. Inhospital mortality was 55.6% with continuous venovenous hemofiltration-high cutoff versus 34.2% with continuous venovenous hemofiltration-standard (adjusted odds ratio, 2.49; 95% CI, 0.81-7.66; p = 0.191). There was no significant difference in time to cessation of norepinephrine (p = 0.358), time to cessation of hemofiltration (p = 0.563), and filter life (p = 0.21). Serum albumin levels (p = 0.192) were similar and the median dose of IV albumin given was 90 grams (20-212 g) for continuous venovenous hemofiltration-high cutoff and 80 grams (15-132 g) for continuous venovenous hemofiltration-standard (p = 0.252).
CONCLUSIONS: In critically ill patients with acute kidney injury, continuous venovenous hemofiltration-high cutoff did not reduce the duration of vasopressor support or mortality or change albumin levels compared with continuous venovenous hemofiltration-standard.

Matched MeSH terms: Dopamine/blood
Osmotic Demyelination Syndrome With Evolving Movement Disorders

Tan AH, Lim SY, Ng RX

JAMA Neurol, 2018 07 01;75(7):888-889.
PMID: 29799978 DOI: 10.1001/jamaneurol.2018.0983
Matched MeSH terms: Dopamine Agents/therapeutic use
Fulltext Review on Cross Talk between Neurotransmitters and Neuroinflammation in Striatum and Cerebellum in the Mediation of Motor Behaviour

Abg Abd Wahab DY, Gau CH, Zakaria R, Muthu Karuppan MK, A-Rahbi BS, Abdullah Z, et al.

Biomed Res Int, 2019;2019:1767203.
PMID: 31815123 DOI: 10.1155/2019/1767203

Neurological diseases particularly Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and epilepsy are on the rise all around the world causing morbidity and mortality globally with a common symptom of gradual loss or impairment of motor behaviour. Striatum, which is a component of the basal ganglia, is involved in facilitating voluntary movement while the cerebellum is involved in the maintenance of balance and coordination of voluntary movements. Dopamine, serotonin, gamma-aminobutyric acid (GABA), and glutamate, to name a few, interact in regulating the excitation and inhibition of motor neurons. In another hand, interestingly, the motor loss associated with neurological diseases is possibly resulted from neuroinflammation induced by the neuroimmune system. Toll-like receptors (TLRs) are present in the central nervous system (CNS), specifically and primarily expressed in microglia and are also found on neurons and astrocytes, functioning mainly in the regulation of proinflammatory cytokine production. TLRs are always found to be associated or involved in the induction of neuroinflammation in neurodegenerative diseases. Activation of toll-like receptor 4 (TLR4) through TLR4 agonist, lipopolysaccharide (LPS), stimulation initiate a signaling cascade whereby the TLR4-LPS interaction has been found to result in physiological and behavioural changes including retardation of motor activity in the mouse model. TLR4 inhibitor TAK-242 was reflected in the reduction of the spinal cord pathology along with the motor improvement in ALS mouse. There is cross talk with neuroinflammation and neurochemicals. For example, TLR4 activation by LPS is noted to release proinflammatory cytokines, IL-1β, from microglia that subsequently suppresses GABA receptor activities at the postsynaptic site and reduces GABA synthesis at the presynaptic site. Glial glutamate transporter activities are also found to be suppressed, showing the association between TLR4 activation and the related neurotransmitters and corresponding receptors and transporters in the event of neuroinflammation. This review is helpful to understand the connection between neurotransmitter and neuroinflammation in striatum- and cerebellum-mediated motor behaviour.

Matched MeSH terms: Dopamine/pharmacology
Fulltext Influence of DRD2 Polymorphisms on the Clinical Outcomes of Opioiddependent Patients on Methadone Maintenance Therapy

Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.

J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S787-S803.
PMID: 33828379 DOI: 10.4103/jpbs.JPBS_248_19

Introduction: Dopamine receptor D2 (DRD2) is one of the dopamine receptors that have been studied in relation to opioid dependence. It is possible, therefore, that DRD2 gene (DRD2) polymorphisms influence treatment outcomes of patients with opioid dependence. The objective of this study was to investigate the influence of DRD2 polymorphisms on the clinical outcomes of opioid-dependent patients on methadone maintenance therapy (MMT).
Materials and Methods: Patients with opioid dependence (n = 148) were recruited from MMT clinics. Pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality were assessed using cold pressor test (CPT), Subjective Opiate Withdrawal Scale (SOWS-M), and Pittsburgh Sleep Quality Index (PSQI)-Malay, respectively. Deoxyribonucleic acid (DNA) was extracted from whole blood, and then was used for genotyping of Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms.
Results: Among 148 patients, 8.1% (n = 12), 60.8% (n = 90), 27.7% (n = 41), and 29.1% (n = 43) had at least one risk allele for Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms, respectively. There were no significant differences in pain responses (pain threshold, tolerance, and intensity), SOWS, and PSQI scores between DRD2 polymorphisms.
Conclusion: The common DRD2 polymorphisms are not associated with pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality in patients with opioid dependence on MMT. However, this may be unique for Malays. Additional research should focus on investigating these findings in larger samples and different ethnicity.

Matched MeSH terms: Receptors, Dopamine D2
Fulltext Brain Beta-Catenin Signalling During Stress and Depression

Teo CH, Soga T, Parhar IS

Neurosignals, 2018 02 22;26(1):31-42.
PMID: 29490303 DOI: 10.1159/000487764

Beta-catenin is a protein with dual functions in the cell, playing a role in both adhesion between cells as well as gene transcription via the canonical Wnt signalling pathway. In the canonical Wnt signalling pathway, beta-catenin again plays multiple roles. In the embryonic stage, the regulation of beta-catenin levels activates genes that govern cell proliferation and differentiation. In an adult organism, beta-catenin continues to regulate the cell cycle - as a result over-expression of beta-catenin may lead to cancer. In the brain, dysfunctions in Wnt signalling related to beta-catenin levels may also cause various pathological conditions like Alzheimer's disease, Parkinson's disease, and depression. Beta-catenin can be influenced by stressful conditions and increases in glucocorticoid levels. In addition, beta-catenin can be regulated by neurotransmitters such as serotonin and dopamine. Fluctuations in beta-catenin in brain regions under duress have been associated with depressive-like behaviours. It is theorized that the change in behaviour can be attributed to the regulation of Dicer by beta-catenin. Dicer, a protein that produces micro-RNAs in the cell, is a target gene for beta-catenin. Amongst the micro-RNA that it produces are those involved in stress resilience. In this way, beta-catenin has taken its place in the well-studied biochemistry of stress and depression, and future research into this interesting protein may yet yield fruitful results in that field.

Matched MeSH terms: Dopamine
Discrimination of dopamine by an electrode modified with negatively charged manganese dioxide nanoparticles decorated on a poly(3,4 ethylenedioxythiophene)/reduced graphene oxide composite

Promsuwan K, Soleh A, Saisahas K, Saichanapan J, Kanatharana P, Thavarungkul P, et al.

J Colloid Interface Sci, 2021 Sep;597:314-324.
PMID: 33872888 DOI: 10.1016/j.jcis.2021.03.162

A unique nanocomposite was fabricated using negatively charged manganese dioxide nanoparticles, poly (3,4-ethylenedioxythiophene) and reduced graphene oxide (MnO2/PEDOT/rGO). The nanocomposite was deposited on a glassy carbon electrode (GCE) functionalized with amino groups. The modified GCE was used to electrochemically detect dopamine (DA). The surface morphology, charge effect and electrochemical behaviours of the modified GCE were characterized by scanning electron microscopy, energy dispersive X-ray analysis (EDX), cyclic voltammetry and electrochemical impedance spectroscopy, respectively. The MnO2/PEDOT/rGO/GCE exhibited excellent performance towards DA sensing with a linear range between 0.05 and 135 µM with a lowest detection limit of 30 nM (S/N = 3). Selectivity towards DA was high in the presence of high concentrations of the typical interferences ascorbic acid and uric acid. The stability and reproducibility of the electrode were good. The sensor accurately determined DA in human serum. The synergic effect of the multiple components of the fabricated nanocomposite were critical to the good DA sensing performance. rGO provided a conductive backbone, PEDOT directed the uniform growth of MnO2 and adsorbed DA via pi-pi and electrostatic interaction, while the negatively charged MnO2 provided adsorption and catalytic sites for protonated DA. This work produced a promising biosensor that sensitively and selectively detected DA.

Matched MeSH terms: Dopamine
Fulltext MicroRNA Dysregulation in Parkinson's Disease: A Narrative Review

Nies YH, Mohamad Najib NH, Lim WL, Kamaruzzaman MA, Yahaya MF, Teoh SL

Front Neurosci, 2021;15:660379.
PMID: 33994934 DOI: 10.3389/fnins.2021.660379

Parkinson's disease (PD) is a severely debilitating neurodegenerative disease, affecting the motor system, leading to resting tremor, cogwheel rigidity, bradykinesia, walking and gait difficulties, and postural instability. The severe loss of dopaminergic neurons in the substantia nigra pars compacta causes striatal dopamine deficiency and the presence of Lewy bodies indicates a pathological hallmark of PD. Although the current treatment of PD aims to preserve dopaminergic neurons or to replace dopamine depletion in the brain, it is notable that complete recovery from the disease is yet to be achieved. Given the complexity and multisystem effects of PD, the underlying mechanisms of PD pathogenesis are yet to be elucidated. The advancement of medical technologies has given some insights in understanding the mechanism and potential treatment of PD with a special interest in the role of microRNAs (miRNAs) to unravel the pathophysiology of PD. In PD patients, it was found that striatal brain tissue and dopaminergic neurons from the substantia nigra demonstrated dysregulated miRNAs expression profiles. Hence, dysregulation of miRNAs may contribute to the pathogenesis of PD through modulation of PD-associated gene and protein expression. This review will discuss recent findings on PD-associated miRNAs dysregulation, from the regulation of PD-associated genes, dopaminergic neuron survival, α-synuclein-induced inflammation and circulating miRNAs. The next section of this review also provides an update on the potential uses of miRNAs as diagnostic biomarkers and therapeutic tools for PD.

Matched MeSH terms: Dopamine; Dopaminergic Neurons
Fulltext Polypharmacy in a nine year old boy with Attention Deficit Hyperactivity Disorder and Tourette Syndrome: what worsened the tics?

Wan Salwina Wan Ismail, Aili Hanim Hashim, Kaur, Manveen, Choo, Shell Pin, Fairuz Nazri Abdul Rahman

Malaysian Journal of Medicine and Health Sciences, 2014;10(2):79-81.
MyJurnal

Attention Deficit Hyperactivity Disorder(ADHD) and Tourrete Syndrome(TS) commonly
co-occur, imposing a special challenge in the management. Case report: This is a case of a nine year old boy with ADHD and TS, who had been on methylphenidate, risperidone, fluvoxamine and atomoxetine, alone and in combination. Tics worsened with methylphenidate but improved after its withdrawal, and the addition of risperidone and fluvoxamine. Later, atomoxetine was added which worsened the tics, even when it was removed. Significant improvement in the tics were only obvious when fluvoxamine was taken off. Discussion: The possible roles of dopamine and serotonin neurotransmission, and metabolism of cytochrome P450 D26 in the pathophysiology were discussed. Conclusion: The use of multiple medications need cautious consideration and monitoring in a child patient to avoid unwanted complications and risks.

Matched MeSH terms: Dopamine
Prophylactic low dose dopamine infusion on renal function in ventilated preterm newborns with respiratory distress syndrome

Hassan, H., Quah, B.S., Haider, D., Rostenberghe, H.V.

Malaysian Journal of Paediatrics and Child Health, 1998;10(2):24-33.
MyJurnal

The aim of the study was to determine the effect of pro-phylactic low dose dopamine infusion on renal function in ventilated premature newborns with respiratory dis-tress syndrome (RDS). A prospective, randomised con-trolled trial was conducted, using low dose dopamine [2.5μg/kg/min] in the treatment of preterm babies with gestational age 28-36 weeks requiring mechanical ventilation for RDS within six hours of age. Thirty-six babies were enrolled and 19 babies were randomly assigned to the treatment groups. The renal function after 72 hours for the treatment and control groups respectively were: urine output (ml/kg/hour) 3.3±0.4 and 3.0±0.3 [p=0.55], urine specific gravity 1006±0.6 and 1006±1.0 [p=0.68], fractional excretion of sodium 4.1±0.8 and 2.6±0.4 [p=0.10], fractional excretion of potassium 37.44 ± 5.6 and 16.49 ± 2.2 [p=0.001], glomerular filtration rate (ml/day/1.72m2) 16±2.6 and 25.6±4.5 [p=0.06]. There were no significant differ-ences in the frequency of hypotension, oliguria and sep-sis between the two groups. There were seven deaths (36.8%) in the treatment group (six due to sepsis and one due to prematurity) and two deaths (11.8%) in the control group (both due to sepsis) (p = 0.13). In con-clusion prophylactic low-dose dopamine infusion did not improve the renal function in ventilated premature babies with respiratory distress syndrome. The results of this study do not support the routine use of prophylac-tic low-dose dopamine in ventilated preterm babies with respiratory distress syndrome.

Matched MeSH terms: Dopamine
Lactobacillus paracasei PS23 reduced early-life stress abnormalities in maternal separation mouse model

Liao JF, Hsu CC, Chou GT, Hsu JS, Liong MT, Tsai YC

Benef Microbes, 2019 Apr 19;10(4):425-436.
PMID: 30882243 DOI: 10.3920/BM2018.0077

Maternal separation (MS) has been developed as a model for inducing stress and depression in studies using rodents. The concept of the gut-brain axis suggests that gut health is essential for brain health. Here, we present the effects of administration of a probiotic, Lactobacillus paracasei PS23 (PS23), to MS mice against psychological traits including anxiety and depression. The administration of live and heat-killed PS23 cells showed positive behavioural effects on MS animals, where exploratory tendencies and mobility were increased in behavioural tests, indicating reduced anxiety and depression compared to the negative control mice (P<0.05). Mice administered with both live and heat-killed PS23 cells also showed lower serum corticosterone levels accompanied by higher serum anti-inflammatory interleukin 10 (IL-10) levels, compared to MS separated mice (P<0.05), indicating a stress-elicited response affiliated with increased immunomodulatory properties. Assessment of neurotransmitters in the brain hippocampal region revealed that PS23 affected the concentrations of dopaminergic metabolites differently than the control, suggesting that PS23 may have improved MS-induced stress levels via neurotransmitter pathways, such as dopamine or other mechanisms not addressed in the current study. Our study illustrates the potential of a probiotic in reversing abnormalities induced by early life stress and could be an alternative for brain health along the gut-brain axis.

Matched MeSH terms: Dopamine
Fulltext Cellular Localization of gdnf in Adult Zebrafish Brain

Wong CED, Hua K, Monis S, Norazit A, Noor SM, Ekker M

Brain Sci, 2020 May 11;10(5).
PMID: 32403347 DOI: 10.3390/brainsci10050286

Glial cell line-derived neurotrophic factor (GDNF) was initially described as important for dopaminergic neuronal survival and is involved in many other essential functions in the central nervous system. Characterization of GDNF phenotype in mammals is well described; however, studies in non-mammalian vertebrate models are scarce. Here, we characterized the anatomical distribution of gdnf-expressing cells in adult zebrafish brain by means of combined in situ hybridization (ISH) and immunohistochemistry. Our results revealed that gdnf was widely dispersed in the brain. gdnf transcripts were co-localized with radial glial cells along the ventricular area of the telencephalon and in the hypothalamus. Interestingly, Sox2 positive cells expressed gdnf in the neuronal layer but not in the ventricular zone of the telencephalon. A subset of GABAergic precursor cells labeled with dlx6a-1.4kbdlx5a/6a: green fluorescence protein (GFP) in the pallium, parvocellular preoptic nucleus, and the anterior and dorsal zones of the periventricular hypothalamus also showed expression with gdnf mRNA. In addition, gdnf signals were detected in subsets of dopaminergic neurons, including those in the ventral diencephalon, similar to what is seen in mammalian brain. Our work extends our knowledge of gdnf action sites and suggests a potential role for gdnf in adult brain neurogenesis and regeneration.

Matched MeSH terms: Dopamine; Dopaminergic Neurons
Treatment of the Hypogonadal Infertile Male-A Review

Ho CC, Tan HM

Sex Med Rev, 2013 May;1(1):42-49.
PMID: 27784559 DOI: 10.1002/smrj.4

INTRODUCTION: Testosterone treatment for hypogonadism is detrimental for men in reproductive age as it impairs spermatogenesis, and therefore affects fertility. It is, therefore, not indicated in men with hypogonadism and infertility.
AIM: The aim of this review is to analyze current data regarding options of treatment for men with hypogonadism and infertility.
MAIN OUTCOMES MEASURES: A comprehensive review of the current literature on management of infertility among hypogonadal men.
METHODS: A literature search using PubMed from 1980 to 2012 was done on articles published in the English language. The following medical subject heading terms were used: "infertility," "infertile," "hypogonadism;" "testosterone deficiency" and "men" or "male;" and "treatment" or "management."
RESULTS: The options for hypogonadal testicular failure are limited. Hormonal treatment is by and large ineffective. For secondary hypogonadism (hypogonadotropic/normogonadotropic hypogonadism), the options include gonadotropin-releasing hormone, human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), and anti-estrogens and aromatase inhibitors. Dopamine antagonist is indicated for prolactinoma. Artificial reproductive technique is indicated for primary testicular failure and also when medical therapy fails.
CONCLUSION: The most suitable option with the current data available is hCG with or without hMG/FSH. Testosterone supplementation should be avoided, but if they are already on it, it is still possible for a return of normal sperm production within 1 year after discontinuing testosterone. Ho CCK and Tan HM. Treatment of the hypogonadal infertile male-A review. Sex Med Rev 2013;1:42-49.

Matched MeSH terms: Dopamine Antagonists
The oral administration of Lotus corniculatus L. attenuates acute and chronic pain models in male rats

Jabbari S, Zakaria ZA, Ahmadimoghaddam D, Mohammadi S

J Ethnopharmacol, 2024 Jan 30;319(Pt 1):117181.
PMID: 37734474 DOI: 10.1016/j.jep.2023.117181

ETHNOPHARMACOLOGICAL RELEVANCE: Lotus corniculatus L. (Fabaceae) traditionally used in Persian folk medicine to heal peritoneal inflammation and back pain.
AIM OF THE STUDY: To explore the antinociceptive (acute pain) and anti-neuropathic (chronic pain) activities of Lotus corniculatus leaves essential oil (LCEO) in addition to uncovering the possible mechanisms of antinociception.
MATERIALS AND METHODS: LCEO as well as the pure oleanolic acid (OA) compound, were assayed for their effects on acute (formalin induced paw licking test or FIPT) and chronic (cervical contusion injury models on the fifth cervical vertebra or CCS; 14-day intervals) pain. The possible involvements of NO-cGMP-K+ channel, TRPV, dopamine, cannabinoid, PPAR, adrenergic, and opioid mechanisms in the antinociceptive activity of LCEO have studied by formalin test. The levels of p53 and inflammatory markers were measured using a streptavidin biotin immune peroxidase complex and ELISA methods, respectively.
RESULTS: The LCEO and OA exerted antinociceptive activity in the first-phase of FIPT. Pretreatment with antagonists of TRPV1, dopamine D2, cannabinoid type1 and 2, and NO-cGMP-K+ channel blockers (glibenclamide, L-NAME and methylene blue) attenuated the antinociceptive effect of LCEO in FIPT. In addition, LCEO and OA meaningfully reduced hyperalgesia (days 6-14) and mechanical allodynia (days 2-14) in the CCS model. LCEO suppressed the apoptotic marker (p53) in CCS model and also ameliorated IL-2, TNF-α, and IL-1 in the spinal cord.
CONCLUSION: Finally, LCEO inhibited acute (possibly via the modulation of opioid, TRPV, dopamine, cannabinoid mechanisms as well as NO-cGMP-K+ channel) and chronic pain (via suppressing apoptotic and inflammatory markers) in male rats. The results also suggest that OA has analgesic activity against acute and chronic pain conditions.

Matched MeSH terms: Dopamine
Fulltext Involvement of monoaminergic system in the antidepressant-like effect of aqueous extract of Channa striatus in mice

Saleem AM, Taufik Hidayat M, Jais AM, Fakurazi S, Moklas MA, Sulaiman MR, et al.

Eur Rev Med Pharmacol Sci, 2013;17(15):2019-22.
PMID: 23884821

BACKGROUND: In our previous study, the aqueous extract of Channa striatus (family: Channidae) fillet (AECSF) showed an antidepressant-like effect in mice. However, the mechanism of the antidepressant-like effect is unknown.
AIM: The objective of this study was to explore the involvement of monoamines in the antidepressant-like effect of AECSF in mice.
MATERIALS AND METHODS: AECSF was prepared by steaming the fillets of C. striatus. The male ICR mice were pretreated with various monoaminergic antagonists viz., p-chlorophenylalanine (100 mg/kg, i.p.), prazosin (1 mg/kg, i.p.) and yohimbine (1 mg/kg, i.p.), SCH23390 (0.05 mg/kg, s.c.) and sulpiride (50 mg/kg, i.p.) followed by treatment with AECSF and tested in tail suspension test (TST). Two-way ANOVA with Tukey test were used at p < 0.05 for significance.
RESULTS: The pretreatments with p-chlorophenylalanine, prazosin and yohimbine, but not with SCH23390 and sulpiride, were able to reverse the antidepressant-like effect of AECSF in TST.
CONCLUSIONS: The antidepressant-like effect of AECSF may be mediated through the serotonergic and noradrenergic systems and not through the dopaminergic system.

Matched MeSH terms: Dopamine D2 Receptor Antagonists/pharmacology
Restless legs syndrome: pathophysiology and modern management

Nagandla K, De S

Postgrad Med J, 2013 Jul;89(1053):402-10.
PMID: 23524988 DOI: 10.1136/postgradmedj-2012-131634

Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is characterised by an irresistible urge to move the legs that significantly affects the quality of life of the patient. Prevalence in the general population is 5-25% and it is twice as prevalent in women as in men. RLS is the most common movement disorder in pregnancy with a fourfold increased risk of developing this disorder later in life. The pathophysiology of RLS is centred on dopaminergic dysfunction, reduced central nervous system iron, genetic linkages, or alteration in neurotransmitters such as hypocretins, endorphins levels and immune dysfunction and inflammatory mechanisms. With the emergence of new evidence, there are changes to the previous treatment recommendations for RLS. There is sufficient evidence to conclude that dopamine agonists such as rotigotine transdermal patch, pramipexole, ropinirole, gabapentin enacarbil, pregabalin and gabapentin are effective in the short-term treatment of RLS and rotigotine, followed by gabapentin enacarbil, ropinirole, pramipexole and gabapentin for long-term treatment. Based on expert consensus, the recommendation for daily RLS is dopamine agonists or gabapentin or low-potency opioids. Levodopa is less preferred for treating daily RLS due to its high risk of augmentation. For intermittent RLS, it is levodopa or dopamine agonists or low-potency opioids or benzodiazepines. For refractory RLS, the choice is to change to gabapentin or a different dopamine agonist, addition of a second agent like gabapentin or benzodiazepine to the existing drug or changing to a high-potency opioid or tramadol. Medications with safety record in pregnancy include opioids and antiepileptics such as carbamazepine and gabapentin. There are concerns that patients with RLS are at risk for metabolic deregulation, autonomic dysfunction and cardiovascular morbidity. However, a recent study concluded that RLS is not associated with increased risk of cardiovascular complications.

Matched MeSH terms: Dopamine Agonists/therapeutic use*
Inhibition of Ang II and renal sympathetic nerve influence dopamine-and isoprenaline-induced renal haemodynamic changes in normal Wistar-Kyoto and spontaneously hypertensive rats

Abdulla MH, Sattar MA, Abdullah NA, Hazim AI, Anand Swarup KR, Rathore HA, et al.

Auton Autacoid Pharmacol, 2008 Oct;28(4):95-101.
PMID: 18778332 DOI: 10.1111/j.1474-8673.2008.00422.x

1. This study was undertaken to elucidate the effects of inhibiting the renin-angiotensin system (RAS) with losartan, and acute unilateral renal denervation on renal haemodynamic responses to intrarenal administration of vasoconstrictor doses of dopamine and vasodilator doses of isoprenaline in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Acute unilateral renal denervation of the left kidney in rats was confirmed by a drop in the renal vasoconstrictor response to renal nerve stimulation (P < 0.05) along with diuresis and natriuresis. Rats were pretreated with losartan for 7 days and thereafter animals fasted overnight were anaesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and acute renal haemodynamic responses studied. 3. Dose-response curves were constructed for dopamine and isoprenaline that induced falls or increases in renal blood flow, respectively. It was observed that renal vascular responses were greater in the denervated as compared with rats with intact renal nerves (all P < 0.05). Dopamine-induced renal vasoconstrictor responses were markedly lower in losartan-treated denervated WKY and SHR compared with their untreated counterparts (all P < 0.05). It was also observed that in losartan-treated and denervated WKY rats the vasodilatory responses to isoprenaline were markedly lower compared with untreated rats (all P < 0.05). However, in SHR, under the same conditions, there was no difference in the renal response to isoprenaline whether or not rats were treated with losartan (P > 0.05). 4. The data obtained showed that the renal vasoconstrictor effect of dopamine depends on intact renal nerves and RAS in WKY and SHR. Isoprenaline responses were likewise sensitive to renal denervation and RAS inhibition in WKY rats but not SHRs. Our observations reveal a possible relationship between renal AT(1) receptors and alpha(1)-adrenoceptors in WKY and SHR. There is also evidence to suggest an interaction between renal beta-adrenoceptors and AT(1) receptors in WKY rats.

Matched MeSH terms: Dopamine/pharmacology*
Fulltext Amphetamine type stimulant (ATS) induced psychosis: A rising problems in Malaysia

Ahmad, H.S.

Malaysian Journal of Psychiatry, 2008;17(2):1-4.
MyJurnal

The past decade has seen a marked increase in the popularity of ATS use, particularly methamphetamine, within East Asia,and the Pacific region. In Malaysia, the National Anti Drug Agency has identified 8,870 addicts (from January till August 2008) out of which 1,126 was ATS dependence. During the same period, the police have arrested 46,388 people under the Dangerous Drug Act 1952. They also has seize 283kg of syabu, 545kg of ecstacy powder, 66194 tablets of esctacy pills and 222,376 tablets of yaba pills from Jan till August this year. The occurrence of psychosis arising from the use of ATS was first reported in the late 1930's. With growing ATS use, particularly methamphetamine, ATS-induced psychosis has become a major impact on public health.Symptoms of ATS-induced psychosis: Methamphetamine use produces a variety of effects, ranging from irritability, to physical aggression, hyperawareness, hypervigilance, and psychomotor agitation. Repeated or high-dose use of the stimulant can cause drug-induced psychosis resembling paranoid schizophrenia, characterized by hallucinations, delusions and thought disorders. When used in long term, methamphetamine may lead to development of psychiatric symptoms due to dopamine depletion in the striatum. The most common lifetime psychotic symptoms among methamphetamine psychotic patients - as reported in a cross-country study involving Australia, Japan, the Philippines and Thailand - are persecutory delusion, auditory hallucinations, strange or unusual beliefs and thought reading. Those patients were also reported to suffer from impaired speech, psychomotor retardation, depression and anxiety. An ATS psychosis can be distinguished from primary psychotic disorders by time. In ATS-induced psychosis symptoms usually resolve after the drug is discontinued. If symptoms do not resolve within 2 weeks after cessation of stimulant use, a primary psychiatric disorder should be suspected. When compared with other stimulants, such as cocaine, psychosis is induced more commonly by ATS, possibly due to the longer duration of action produced by amphetamines.For example, while smoking cocaine produces a high that lasts for 20-30 minutes, smoking methamphetamine produces a high that lasts 8-24 hours. Other symptoms of ATS-induced psychosis reported include affective blunting,(6) violent behavior, and self-mutilation and self-injurious behavior.

Matched MeSH terms: Dopamine
Ameliorative Effect of Curcumin on Olanzapine-induced Obesity in Sprague-Dawley Rats

Parasuraman S, Zhen KM, Banik U, Christapher PV

Pharmacognosy Res, 2017 Jul-Sep;9(3):247-252.
PMID: 28827965 DOI: 10.4103/pr.pr_8_17

OBJECTIVE: To evaluate the effect of curcumin on olanzapine-induced obesity in rats.

MATERIALS AND METHODS: Sprague-Dawley (SD) rats were used for experiments. The animals were divided into six groups, namely, normal control, olanzapine control, betahistine (10 mg/kg), and curcumin 50, 100, and 200 mg/kg treated groups. Except the normal control group, all other animals were administered with olanzapine 4 mg/kg intraperitoneally to induce obesity. The drugs were administered once daily, per oral for 28 days. During the experiment, body weight changes and behavior alterations were monitored at regular intervals. At the end of the experiment, blood sample was collected from all the experimental animals for biochemical analysis. Part of the liver and kidney tissues was harvested from the sacrificed animals and preserved in neutral formalin for histopathological studies.

RESULTS: Curcumin showed a significant reduction in olanzapine-induced body weight gain on the rats and improved the locomotor effects. The effect of curcumin on olanzapine-induced body weight gain is not comparable with that of betahistine.

CONCLUSION: This study has shown metabolic alteration effect of curcumin on olanzapine, an antipsychotic drug, treated SD rats.

SUMMARY: Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia and bipolar disorder. Obesity is an adverse effect of olanzapine, and the present study was made an attempt to study the effect of curcumin on olanzapine-induced obesity in rats. In this present study, curcumin significantly reduced olanzapine-induced body weight gain in rats. Abbreviations Used: 5HT: 5-hydroxytryptamine, ALP: Alkaline phosphatase, ALT: Alanine transaminase, ANOVA: Analysis of variance, AST: Aspartate transaminase, CMC: Carboxymethyl cellulose, D: Dopamine, H and E: Hematoxylin and Eosin stain, H: Histamine, HDL-C: Highdensity lipoprotein cholesterol, IP: Intraperitoneal, MAO: Monoamine oxidase, NaOH: Sodium hydroxide, SD rats: Sprague Dawley rats, TCs: Total cholesterols, TG: Triglyceride.

Matched MeSH terms: Dopamine
Fulltext Brain Cortical and Hippocampal Dopamine: A New Mechanistic Approach for Eurycoma longifolia Well-Known Aphrodisiac Activity and Its Chemical Characterization

Ezzat SM, Ezzat MI, Okba MM, Hassan SM, Alkorashy AI, Karar MM, et al.

Evid Based Complement Alternat Med, 2019;2019:7543460.
PMID: 31275418 DOI: 10.1155/2019/7543460

Eurycoma longifolia Jack (Fam.: Simaroubaceae), known as Tongkat Ali (TA), has been known as a symbol of virility and sexual power for men. Metabolic profiling of the aqueous extract of E. longifolia (AEEL) using UPLC-MS/MS in both positive and negative modes allowed the identification of seventeen metabolites. The identified compounds were classified into four groups: quassinoids, alkaloids, triterpenes, and biphenylneolignans. AEEL is considered safe with oral LD50 cut-off >5000 mg/kg. Oral administration of 50, 100, 200, 400, or 800 mg/kg of AEEL for 10 consecutive days to Sprague-Dawley male rats caused significant reductions in mounting, intromission, and ejaculation latencies and increased penile erection index. AEEL increased total body weight and relative weights of seminal vesicles and prostate. Total and free serum testosterone and brain cortical and hippocampal dopamine content was significantly elevated in treated groups with no significant effects on serotonin or noradrenaline content.

Matched MeSH terms: Dopamine

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