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The Journal of Pharmacology and... Apr 2018Although dystonia is often associated with abnormal dopamine neurotransmission, dopaminergic drugs are not currently used to treat dystonia because there is a general...
Although dystonia is often associated with abnormal dopamine neurotransmission, dopaminergic drugs are not currently used to treat dystonia because there is a general view that dopaminergic drugs are ineffective. However, there is little conclusive evidence to support or refute this assumption. Therefore, to assess the therapeutic potential of these compounds, we analyzed results from multiple trials of dopamine receptor agonists in patients with idiopathic dystonias and also tested the efficacy of dopamine receptor agonists in a mouse model of generalized dystonia. Our results suggest that dopamine receptor agonists were effective in some, but not all, patients tested. Further, the mixed D1/D2 dopamine receptor agonist apomorphine was apparently more effective than subtype selective D2 dopamine receptor agonists. However, rigorously controlled trials are still needed. In a mouse model of dystonia, a selective D1 dopamine receptor agonist was not effective while a selective D2 dopamine receptor had modest efficacy. However, when combined, these receptor-selective agonists acted synergistically to ameliorate the dystonia. Coactivation of D1 and D2 dopamine receptors using apomorphine or by increasing extracellular concentrations of dopamine was also effective. Thus, results from both clinical trials and tests in mice suggest that coactivation of D1 and D2 dopamine receptors may be an effective therapeutic strategy in some patients. These results support a reconsideration of dopamine receptors as targets for the treatment of dystonia, particularly because recent genetic and diagnostic advances may facilitate the identification of the subtypes of dystonia patients who respond and those who do not.
Topics: Animals; Biogenic Monoamines; Dopamine Agonists; Dystonia; Female; Humans; Male; Mice; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 29348266
DOI: 10.1124/jpet.117.246348 -
European Journal of Endocrinology Apr 2007The dopaminergic system has a pivotal role in the central nervous system but also plays important roles in the periphery, mainly in the endocrine system. Dopamine exerts... (Review)
Review
The dopaminergic system has a pivotal role in the central nervous system but also plays important roles in the periphery, mainly in the endocrine system. Dopamine exerts its functions via five different receptors, named D(1)-D(5), belonging to the category of G protein coupled membrane receptors. Dopamine receptors are heterogeneously expressed in different cells, tissues and organs, where they stimulate or inhibit different functions, including neurotransmission and hormone synthesis and secretion. In particular, the dopamineric system has a pivotal role in the physiological regulation of the hypothalamus-pituitary-adrenal axis. Recent data have demonstrated the expression and function of dopamine receptors not only in endocrine organs but also in endocrine tumors, mainly those belonging to the hypothalamus-pituitary-adrenal axis, and also in the so-called 'neuroendocrine' tumors. These data confirm the important role of the dopaminergic system in this endocrine axis, as well as in the neuroendocrine system. This review summarizes the main structural and functional characteristics of dopamine receptors, emphasizing the most recent novelties, and focused on the physiological and pathological regulation of the hypothalamus-pituitary-adrenal axis by the dopaminergic system. In addition, the recent findings on the relationship between dopamine receptors and neuroendocrine tumors are summarized.
Topics: Humans; Hypothalamo-Hypophyseal System; Neuroendocrine Tumors; Pituitary-Adrenal System; Receptors, Dopamine
PubMed: 17413183
DOI: 10.1530/eje.1.02353 -
Advances in Experimental Medicine and... 1986
Review
Topics: Amygdala; Animals; Behavior, Animal; Benzazepines; Binding Sites; Brain; Brain Chemistry; Dopamine; Dopamine Antagonists; Injections, Intraperitoneal; Rats; Receptors, Dopamine; Receptors, Dopamine D1
PubMed: 2947430
DOI: 10.1007/978-1-4684-5191-7_4 -
Advances in Experimental Medicine and... 1986
Review
Topics: Animals; Apomorphine; Benzazepines; Brain; Dopamine; Dopamine Antagonists; Dose-Response Relationship, Drug; Electrophysiology; Injections, Intravenous; Neurons; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Substantia Nigra
PubMed: 2947427
DOI: 10.1007/978-1-4684-5191-7_11 -
International Review of Neurobiology 2011Orofacial movements involve complex processes that include generators for down-stream patterns, with up-stream regulatory mechanisms. While the neurotransmitter dopamine... (Review)
Review
Orofacial movements involve complex processes that include generators for down-stream patterns, with up-stream regulatory mechanisms. While the neurotransmitter dopamine plays a fundamental role, the role of individual dopamine receptor subtypes and their associated transduction mechanisms is unclear. Here we review systematic, comparative studies of orofacial function in mutant mice with "knockout" of D1, D2, D3, D4 or D5 receptors, or of their critical transduction component DARPP-32 at four levels: general orofacial behaviors within the mouse repertoire, as assessed naturalistically; individual components of orofacial movement, as assessed under non-naturalistic conditions; each of the above, as assessed also under challenge with a D1-like vs a D2-like agonist. Studies in these "knockouts" provide novel insights into the motoric "building blocks" that regulate orofacial function.
Topics: Animals; Dopamine; Dopamine Agents; Face; Humans; Mice; Mice, Knockout; Movement; Receptors, Dopamine; Sex Characteristics; Signal Transduction
PubMed: 21708306
DOI: 10.1016/B978-0-12-385198-7.00002-3 -
American Journal of Physiology. Heart... Feb 2008Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and by interacting with vasoactive hormones/humoral... (Review)
Review
Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and by interacting with vasoactive hormones/humoral factors, such as aldosterone, angiotensin, catecholamines, endothelin, oxytocin, prolactin pro-opiomelancortin, reactive oxygen species, renin, and vasopressin. Dopamine receptors are classified into D(1)-like (D(1) and D(5)) and D(2)-like (D(2), D(3), and D(4)) subtypes based on their structure and pharmacology. In recent years, mice deficient in one or more of the five dopamine receptor subtypes have been generated, leading to a better understanding of the physiological role of each of the dopamine receptor subtypes. This review summarizes the results from studies of various dopamine receptor mutant mice on the role of individual dopamine receptor subtypes and their interactions with other G protein-coupled receptors in the regulation of blood pressure.
Topics: Animals; Blood Pressure; Dopamine; Hypertension; Mice; Mice, Knockout; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4; Receptors, Dopamine D5
PubMed: 18083900
DOI: 10.1152/ajpheart.01036.2007 -
Annals of the New York Academy of... 1988
Review
Topics: Amphetamine; Animals; Behavior; Brain; Dopamine; Drug Tolerance; Dyskinesia, Drug-Induced; Humans; Receptors, Dopamine; Stereotyped Behavior
PubMed: 3059930
DOI: 10.1111/j.1749-6632.1988.tb42116.x -
Progress in Drug Research. Fortschritte... 1997
Review
Topics: Amino Acid Sequence; Animals; Antipsychotic Agents; Genetic Linkage; Humans; Molecular Sequence Data; RNA, Messenger; Receptors, Dopamine; Signal Transduction
PubMed: 9204687
DOI: 10.1007/978-3-0348-8861-5_7 -
Pharmacogenomics Aug 2001The elucidation of the assumed genetic contribution to the predisposition towards schizophrenia is a scientifically challenging enterprise with considerable impact on... (Review)
Review
The elucidation of the assumed genetic contribution to the predisposition towards schizophrenia is a scientifically challenging enterprise with considerable impact on therapeutic possibilities. A pharmacogenetic approach, targeted to the clinical response to medication, provides a promising alternative as a means of investigation, with the prospect of gaining knowledge about the disease and of developing an individually tailored medical treatment. This review will focus on dopamine receptor genes which have, due to the dopamine hypothesis of schizophrenia, been a prime target in pharmacogenetic studies of schizophrenia. The current status of the studies results will be displayed and future prospects will be discussed.
Topics: Humans; Pharmacogenetics; Polymorphism, Genetic; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4; Schizophrenia
PubMed: 11535113
DOI: 10.1517/14622416.2.3.251 -
International Journal of Developmental... Nov 2000The family of five dopamine receptors subtypes activate cellular effector systems through G proteins. Historically, dopamine receptors were thought to only stimulate or... (Review)
Review
The family of five dopamine receptors subtypes activate cellular effector systems through G proteins. Historically, dopamine receptors were thought to only stimulate or inhibit adenylyl cyclase, by coupling to either G(s)alpha or G(i)alpha, respectively. Recent studies in transfected cells, reviewed here, have shown that multiple and highly diverse signaling pathways are activated by specific dopamine receptor subtypes. This multiplicity of signaling responses occurs through selective coupling to distinct G proteins and each of the receptors can interact with more than one G protein. Although some of the multiple coupling of dopamine receptors to different G proteins occurs from within the same family of G proteins, these receptors can also couple to G proteins belonging to different families. Such multiple interactions between receptors and G proteins elicits functionally distinct physiological effects which acts to enhance and subsequently suppress the original receptor response, and to activate apparently distinct signaling pathways. In the brain, where coexpression of functionally distinct receptors in heterogeneous cells further adds to the complexity of dopamine signaling, minor alterations in receptor/G protein coupling states during either development or in adults, may underlie the imbalanced signaling seen in dopaminergic-linked diseases such as schizophrenia, Parkinson's disease and attention deficit hyperactivity disorder.
Topics: Animals; GTP-Binding Proteins; Humans; Nervous System; Receptors, Dopamine
PubMed: 10978845
DOI: 10.1016/s0736-5748(00)00033-2