الفهرس 
Introduction and Aim of The WorkOnly 14 pages are availabe for public view
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Abstract
Dopamine receptors (DR) are one of the major neurotransmitter receptors present in human brain. Malfunctioning of these receptors is well established to trigger many neurological and psychiatric disorders (Podder A et al., 2014) as well as its enormous neuroendocrine link, that rendered dopamine receptors intertwining with various endocrine diseases. The previous chapter demonstrated the diverse effects of dopamine receptors upon various aspects of Endocrinology and Metabolism from which we can deduce and speculate prospects for future clinical utility of dopamine receptors agonists . Three aspects for Dopamine receptors in Endocrinology and Metabolism have 1. First its role of D2 receptors agonist Cabergoline in ACTH secreting tumours whether pituitary , ectopic or within the context of Nelson syndrome . Some studies have been conducted over the past decade , a recent systematic review explored the studies conducted on different old and new agents for medical treatment of ACTH secreting tumors . Of the studies conducted on cabergoline four were eligible to be included in a recent systematic analysis that showed that cabergoline achieved a 50% response rate in these selected studies as compared to 29% achieved by the new somatostatin analogue pasirotide that preferentially binds to the somatostatin type 5 receptor, which is expressed in corticotrope tumors. Yet in this systematic review the study design conducted for pasirotide was a double blinded multicenter RCT and two prospective cohort trials which strengthened the grade of evidence for pasirotide compared to cabergoline studies which were three prospective cohort studies and one retrospective cases series . Thus the grade of evidence was moderate for pasirotide and low for cabergoline while studies conducted using bromocreptine were deemed ineligible (Gadelha MR et al., 2014). Thus Pasireotide have been approved in the EU and US for the treatment of adult patients with CD for whom surgery has failed or is not an option, on the basis of these Phase III trial results , whereas cabergoline has been approved in Europe only . It should be noted that performing large-scale clinical trials in this patient population presents a huge challenge, primarily because of the rarity of the disease, but also because of problems with obtaining accurate estimates of hypercortisolism and the lack of standardization in assay methods. Therefore, studies in CD are unlikely to achieve the highest ratings when employing standardized criteria such as those used in a GRADE analysis (Gadelha MR., 2014). In conclusion further well designed and conducted trials should be perused regarding using Cabergoline in ACTH secreting tumors as well as neuroendocrine tumors documented to express D2 receptors . Also recent studies of combination therapy by administration of both types of compounds yielded promising results. These clinical reports of enhanced efficacy of combination therapy with SSTR- and dopamine agonist treatment (originally initiated for pituitary adenoma therapy in suppressing growth hormone hypersecretion) lead to the novel concept of somatostatin-dopamine chimeric molecules (Eckstein N et al., 2014). Studies on different tumor models, including pituitary adenomas, revealed a higher potency of BIM-23A779, BIM-23A760, and BIM-23A781 (chimeric molecules containing both SST and dopamine structural elements) in controlling tumor cell growth . Further studies in CD patients are needed (Fleseriu M and Cuevas-Ramos D, 2014).
2. Another aspect of D2 receptor agonist is its upcoming role in diabetes Bromocriptine-QR (a quick-release formulation of bromocriptine mesylate), a dopamine D2 receptor agonist that reduces postprandial hyperglycemia without raising plasma insulin levels, was approved by the US Food and Drug Administration for the treatment of hyperglycemia in type 2 diabetes mellitus (T2DM) patients in May 2009 under the trade name Cycloset. A recent study conducted to explore cardiovascular safety revealed a 39% and 52% relative risk reductions in the CV death-inclusive composite cardiovascular and major cardiovascular events end points, respectively, among bromocriptine-QR versus placebo subjects in the Cycloset Safety Trial corroborate . This adds a potentially safe drug regarding cardiovascular profile to the growing armamentarium of oral hypoglycemic agents (Gaziano JM et al., 2012). 3. Third aspect for future implications of Dopamine receptors effect is its role in PCOS and pubertal development . Although the pathogenesis of PCOS is still controversial, an array of plausible pathophysiologies has emerged over the last several decades of Studies. Dopamine deficiency has been considered in the pathogenesis of hypothalamic abnormalities in PCOS. Some women with PCOS exhibit enhanced sensitivity to systemic dopamine infusions (Barontini M et al., 2001). Recent and earlier studies showed a promising effect for cabergoline in PCOS and ovarian hyperstimulation syndrome (Ajossa S et al., 1999; Ajossa S et al ., 2002; Mohammadbygi R et al., 2013). Also much research has emerged lately on the mutual effect of gonadal steroids on the dopaminergic neurons expression during adolescence and the profound effect on risk taking behavior and reward system that it is deeply involved in addiction tendency(Kuhn C et al., 2010). Finally a recent interesting study showed that The dopamine receptor D4 gene (DRD4) has been linked to sexual activity and other forms of appetitive behavior, particularly for male youth and in combination with environmental factors (Kogan SM et al., 2014).