ChemInform Abstract: Novel 4,5,6,7-Tetrahydrobenzothiazole Dopamine Agonists Display very Low Stereoselectivity in Their Interaction with Dopamine Receptors.

ChemInform ◽  
2010 ◽  
Vol 23 (18) ◽  
pp. no-no
Author(s):  
J. C. JAEN ◽  
B. W. CAPRATHE ◽  
L. D. WISE ◽  
S. J. SMITH ◽  
T. A. PUGSLEY ◽  
...  
2009 ◽  
Vol 43 (9) ◽  
pp. 1426-1432 ◽  
Author(s):  
Steven C Stoner ◽  
Megan M Dahmen ◽  
Mignon Makos ◽  
Jessica W Lea ◽  
Lora J Carver ◽  
...  

Background: Traditional treatment approaches for the management of restless legs syndrome (RLS) and Parkinson's disease (PD) include the use of medications that either directly or indirectly increase dopamine levels. In turn, a potential adverse event that could be expected is the development or exacerbation of psychiatric-related symptoms. Objective: To evaluate and describe the incidence of psychosis and associated behavioral features in patients taking ropinirole for RLS or PD. Methods: Patients were identified from a computerized database search of outpatients being treated with ropinirole for 1 of 2 medical conditions: PD or RLS. Data were collected in a retrospective manner from 95 patients who were tracked over the course of their therapy to determine whether psychosis or associated behavioral symptoms developed as a result and whether an intervention was needed to adjust ropinirole dosing or if additional medications had to be added to control features associated with psychosis. Results: A total of 284 patients being treated for RLS or PD were identified; of this group, 95 patients were identified as being treated for PD or RLS with ropinirole. Of the 95 patients being treated with ropinirole, 13 developed psychotic features that required therapeutic intervention with either the use of an antipsychotic or dose adjustment of ropinirole. PD patients included in this study were numerically more likely to develop psychotic features compared with RLS patients; however, the difference was not statistically significant (p = 0.122). The results do suggest that this risk is increased when ropinirole is used as part of a dual therapy approach with dopamine agonists in the treatment of either PD or RLS (p = 0.003). Discussion: Dopamine agonists have long been used as preferred treatment in the management of PD and RLS. When treating either PD or RLS in the psychiatric population, the concern arises that increased activity at dopamine receptors may induce or exacerbate psychiatric features. A potential clinical concern with the use of ropinirole is the potential for patients to develop psychiatric features, although there are few data available to demonstrate whether stimulation of targeted individual dopamine receptors is linked to the development or exacerbation of psychotic features. It is also undetermined whether concurrent antipsychotic treatment provides any protective benefit against psychosis, especially in patients already being treated for psychotic symptoms. Conclusions: Our findings suggest that ropinirole may play a role in inducing or exacerbating psychosis and its associated features, although a number of confounding variables prevent the determination of a clear association and suggest that further investigation is warranted in controlled clinical trials.


Cephalalgia ◽  
1998 ◽  
Vol 18 (4) ◽  
pp. 174-182 ◽  
Author(s):  
A Mascia ◽  
J Qqaacute;fra ◽  
J Schoenen

The dopamine theory of migraine pathogenesis, first proposed by F. Sicuteri in 1977, has attracted renewed interest after an increased frequency of the dopamine D2 receptor (DRD2) gene allele NcoI C was found in patients with migraine with aura. Therefore we reviewed the relevant literature. The most compelling argument favoring an interictal hypersensitivity of dopamine receptors in migraineurs stems from pharmacologic studies of the gastric and autonomic effects of dopaminergic agents such as apomorphine, but none of these studies was blinded and placebo-controlled. Various DRD2 antagonists abort migraine attacks after parenteral administration, while mere is circumstantial evidence that dopamine agonists may be useful for prophylaxis. Most drugs used in these trials, however, lack selectivity for dopamine receptors. Both in pharmacological and therapeutic studies most patients had migraine without aura. We conclude that data suggesting a primary role for the dopaminergic system in migraine pathogenesis are unconvincing. Based on well established interactions between central amines, a reduced release of serotonin between attacks could lower dopamine release which would lead to receptor hypersensitivity.


Cephalalgia ◽  
2007 ◽  
Vol 27 (11) ◽  
pp. 1308-1314 ◽  
Author(s):  
S Akerman ◽  
PJ Goadsby

In the last 30 years dopamine has been considered as playing a role in the pathogenesis of migraine. The literature indicates that migraineurs are hypersensitive to dopamine agonists with respect to some of the premonitory symptoms of migraine such as nausea and yawning. There are various nonspecific dopamine D2 receptor antagonists that show good clinical efficacy in migraine, and also a number of polymorphisms of dopaminergic genes related to migraine. Animal studies have also shown that dopamine receptors are present in the trigeminovascular system, the area believed to be involved in headache pain, and neuronal firing here is reduced by dopamine agonists. There appears to be little effect of dopamine on peripheral trigeminal afferents. We assess some of the limitations of the clinical studies with regard to the therapeutics, and those found in the studies that discovered differences in genetic polymorphisms in migraine, and consider the implications of this on a dopaminergic hypothesis of migraine.


2019 ◽  
Vol 4 (1) ◽  

Long term use of first generation anti-psychotics (FGAs) have been theorized in the formation of motion disorders Tardive Dyskinesia and Akathasia and due to the breakdown in the extra pyramidal system (EPS) located in the Basal Ganglia [1]. The second generation anti-psychotics (SGAs) were sourced to be the “treatment” of TD by blocking dopamine receptors with dopamine agonists of the D2-D5 receptors while also being seen as the genesis of AK. However, the blocking of the receptors in both motion disorders is a theory known as the dopamine blockage theory, despite the intermingle of other neurotransmitters such as Serotonin and Norepinephrine [2]


Author(s):  
Donald B. Calne ◽  
Keith Burton ◽  
Jeff Beckman ◽  
W.R. Wayne Martin

ABSTRACTDopamine agonists have yielded two important advances to our understanding of the basal ganglia – they have facilitated the subdivision of different classes of dopamine receptors, and they have established the fact that important dopaminergic effects can be achieved by activation of dopamine receptors in a manner that is unrelated to anoxal impulse traffic in dopaminergic neurons – a phenomenon similar in its diffuse, slow, characteristics to an endocrine effect.The tangible clinical benefit of dopamine agonists has been evident in patients with prominent dyskinesia or wearing off reactions. It is possible that earlier use of agonists, in low doses combined with similarly low doses of levodopa, may improve the long term treatment of Parkinson’s disease, but as yet there is no firm evidence.In the future, we can expect to see agonists with more prolonged effects, deriving from the formation of active metabolites. We can also hope to gain further insight into the correlations between the various animal models of dopaminomimetic activity, and specific aspects of drug efficacy and toxicity in parkinsonian patients. Such information should allow the design of improved pharmacotherapy.


Author(s):  
X. Lataste

ABSTRACTThe recognition of the dopaminergic properties of some ergot derivatives has initiated new therapeutical approaches in endocrinology as well as in neurology. The pharmacological characterization of the different ergot derivatives during the last decade has largely improved our understanding of central dopaminergic systems. Their development has yielded valuable information on the pharmacology of dopamine receptors involved in the regulatory mechanisms of prolactin secretion and in striatal functions.The clinical application of such new neurobiological concepts has underlined the therapeutical interest of such compounds either in the control of prolactin-dependent endocrine disorders or in the treatment of parkinsonism. Owing to their pharmacological profiles, dopaminergic agonists represent a valuable clinical option especially in the management of Parkinson’s disease in view of the problems arising from chronic L-Dopa treatment.


2007 ◽  
Vol 156 (suppl_1) ◽  
pp. S37-S43 ◽  
Author(s):  
Diego Ferone ◽  
Rosario Pivonello ◽  
Eugenia Resmini ◽  
Mara Boschetti ◽  
Alberto Rebora ◽  
...  

Pituitary tumors can cause symptoms of mass effect and hormonal hypersecretion that can be reversed with surgical resection or debulking of the adenoma, radiotherapy, or medical treatment. Medical treatment is the primary choice for prolactinomas because dopamine agonists are very effective in the treatment of these tumors, with rates of control (tumor size reduction and hormone suppression) as high as 80–90% for microprolactinomas and 60–75% for macroprolactinomas. The function of dopamine receptors in other histotypes of pituitary adenoma is still debated. However, new insights into receptor physiology and the introduction of new clinically available, as well as experimental, compounds have reopened a potential role of dopaminergic drugs in the medical treatment of pituitary tumors. The differences between the effectiveness and the resistance to different dopaminergic agents, the new challenging results from clinical and experimental studies, as well as the future of dopamine agonists in the therapy of pituitary tumors are discussed.


1993 ◽  
Vol 84 (4) ◽  
pp. 357-375 ◽  
Author(s):  
M. R. Lee

Ten years ago the Editorial Board of Clinical Science invited me to write an Editorial Review on dopamine and the kidney. The result was published in 1982 in Volume 62 [1]. It was my hope that it would serve to stimulate other investigators to take up this area of renal physiology and pharmacology and to help to solve some of the problems left unanswered at that time. Since 1982 much has happened: there have been major successes, such as the delineation of the renal and adrenal dopamine receptors, and some relative failures, such as the lack of development of clinically useful peripheral dopamine agonists for use in hypertension and congestive cardiac failure. Nevertheless, continuous progress has been made and it is my task in this Review to try to describe this general advance while not omitting remaining areas of uncertainty. The areas which I will undertake to describe are: 1. The renal receptors for dopamine. 2. The source of dopamine in the urine and its formation in the kidney. 3. The actions of dopamine upon the kidney. 4. The interaction of renal dopamine with other substances. 5. Dopamine formation in hypertensive and oedematous states. 6. The search for specific peripheral dopaminergic agonists of therapeutic utility. 7. Final conclusions and unanswered questions.


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