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Renal, Cardiovascular, and Pulmonary Functions of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
As documented by in vivo and in vitro studies, activation of D1R in resistance arteries by DA at low concentrations normally causes dilation. Treatment of dogs and rats with fenoldopam, a peripheral D1R agonist, decreased blood pressure without activating central DAR [47]. In another study, fenoldopam reduced mean arterial pressure, lowered arterial and venous resistance, and increased cardiac output in rats [48]. At the highest dose, fenoldopam also increased heart rates and reduced the mean circulatory filling pressure, the driving force of venous return. Chronic inhibition of dopamine beta-hydroxylase (DBH), which converts DA to NE, decreased urinary DA and NE in SHR rats, and caused a marked reduction in their blood pressure [49]. The authors postulated that the observed hypotension was due to the combination of reduced circulating NE and increased DA; the treatment itself did not prevent development of the disease in this genetic animal model of hypertension.
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
DOPAMINE BETA HYDROXYLASE, the enzyme involved in the conversion of DOPAMINE to NORADRENALINE. As such, disulfram can be used to inhibit the formation of noradrenaline in neurons. However, its better known medical property probably does not rely on this action. Disulfram is given to patients who have recovered from ALCOHOLISM and who wish to avoid further ALCOHOL ABUSE. Disulfram inhibits (again, by chelation of copper) the activity of the enzyme aldehyde dehyrodgenase, which is involved in the conversion of acetaldehyde to acetate, part of the sequence of alcohol metabolism in the body. Without this enzyme, if alcohol is consumed, levels of acetaldehyde in the body rise and are accompanied by sordid and ghastly effects, including nausea, vomiting and problems with respiration. A single dose of disulfram has effects lasting last for up to 2 weeks, and only a small amount of alcohol is required to trigger the unpleasant consequences. Disulfram therefore helps keep recovered alcoholics away from alcohol by threatening extreme NEGATIVE REINFORCEMENT.
Effects of Antidepressants on Specific Neurotransmitters: Are Such Effects Relevant to Therapeutic Actions?
Published in Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen, Handbook of Depression and Anxiety, 2003
In depression, the monoamine neurotransmitters are thought to play a crucial role and twin, adoption, and family segregation analyses have established that there is a strong, albeit complex, genetic component to the disorder. Thus the enzymes that control the synthesis of these neurotransmitters may be strong candidate genes. In summary, it has been shown that the tryptophan hydroxylase gene is associated with impulsivity and violent suicide and that some investigators have identified an allelic form (the U-allele) that correlates with aggression and anger-related personality traits in some individuals [10]. In another study of patients in Finland, two polymorphic forms of the tryptophan hydroxy-lase gene have been correlated to suicidality [72]. In regard to tyrosine hydroxlase, there is conflicting evidence in the literature regarding the link between different polymorphic forms of this enzyme and depression in patients with bipolar disorder [65]. No evidence of a linkage between the DOPA-decarboxylase and the dopamine-beta-hydroxylase genes and psychiatric disease have so far been found. Clearly this is an important area for future research into the role that abnormal allelic forms of the enzymes and receptors that are involved in neurotransmission may play in depression.
Dopamine β hydroxylase as a potential drug target to combat hypertension
Published in Expert Opinion on Investigational Drugs, 2020
Sanjay Kumar Dey, Manisha Saini, Pankaj Prabhakar, Suman Kundu
Such attempts during the last few years include the development of inhibitors of mineralocorticoid receptor, antagonists of vasopeptidases, aldosterone synthase, and soluble epoxide hydrolase, activators of natriuretic peptide A and vasoactive intestinal peptide receptor 2, inhibitors of aminopeptidase A, intestinal Na+/H+ exchanger 3 inhibitors, activators of key players of the angiotensin-converting enzyme 2, angiotensin (1–7), Mas receptor axis, vaccines against angiotensin II and its type 1 receptor among others [4]. Nevertheless, there have been no new class of drugs of late which can utilize body’s own BP lowering mechanism with fewer side effects, desired systolic and diastolic BP (SBP and DBP) and the ability to combat resistant hypertension. Dopamine β hydroxylase (DBH), a key enzyme of the dopaminergic pathway, is involved in the sympathetic nervous system (SNS) and plays a central role in regulating BP through dopaminergic receptors [17]. This enzyme is explored in this review as a novel drug target to treat hypertension, including resistant, portal, and pulmonary hypertension. We review the current research progress and available inhibitors of DBH with their advantage and disadvantages. We also outlined a direction for utilizing existing as well as new in silico, in vitro, ex vivo, and in vivo tools for rapid identification and validation of novel inhibitors of DBH.
On the path toward personalized medicine: implications of pharmacogenetic studies of alcohol use disorder medications
Published in Expert Review of Precision Medicine and Drug Development, 2020
Steven J. Nieto, Erica N. Grodin, Lara A. Ray
Alcohol, like most drugs of abuse, increases dopamine release in the ventral striatum. There are five main types of dopamine receptors that are organized into two families, D1-like and D2-like, all of which are G-coupled protein receptors. The Taq1A polymorphism, located downstream of the dopamine receptor 2 (DRD2) and within the Ankyrin Repeat and Kinase Domain Containing 1 (ANKK1) gene, has been shown to moderate treatments in individuals with AUD (see Table 2). Ooteman et al. [49] found that AUD individuals who were A1 homozygotes benefited more from acamprosate versus NTX on cue-induced craving relative to A2 homozygotes, who benefited more from NTX versus acamprosate. In another study of AUD individuals, A1 carriers treated with bromocriptine, a D2 agonist, had lower craving for alcohol relative to A2 homozygotes [69]. Additionally, dopamine can be converted to the neurotransmitter norepinephrine by the enzyme dopamine beta-hydroxylase (DBH). A SNP (rs1611115) in the DBH gene has been shown to moderate NTX responses in AUD individuals. Specifically, NTX-treated T carriers had more abstinence from heavy drinking than those with the CC genotype on NTX [54]. Conversely, NTX-treated C homozygotes had lower abstinence rates compared to placebo-treated C homozygotes. Taken together, genetic variants in the catecholamine system may help identify individuals with AUD who will respond better or do worse on NTX relative to placebo.
Antidepressants Promote and Prevent Cancers
Published in Cancer Investigation, 2020
Francis Lavergne, Therese M. Jay
Stress like sleep deprivation (70) increases serum BDNF. Sympathetic stimulation, induced via continual noise and exhaustive exercise, enhances thrombopoiesis. Both stress stimulations are shown to elevate peripheral platelet levels at day 3 (p < .05) and day 7 (p < .01) in normal mice. On the contrary, this effect was not seen in mice lacking norepinephrine and epinephrine due to dopamine β-hydroxylase–deficiency (Dbh−/−) (69). In the bone marrow, stress stimulates platelet production. This finding is unexpected since stress usually decreases neurogenesis in the brain, at least in the hippocampus and prefrontal cortex. Stress, in the bone marrow, induces a defensive reaction, such as an increase in platelet production.