Treatment dopamine agonists

A number of azetidine-based compounds have been disclosed in patent applications from Aventis Pharma for CBi-modulated treatment of diseases such as obesity, Parkinson s disease, schizophrenia, respiratory and neurological diseases [330-334]. Compound (556) was specifically claimed for use in two formulation patent applications [330, 331] for a stable semi-solid composition and oral emulsion composition, respectively. The optional coadministration of an agent that activates norepinephrinergic and se-rotoninergic neurotransmission (for example, sibutramine) or dopaminergic neurotransmission was also claimed for the treatment of obesity. The optional use of a dopamine agonist (for example, levodopa) was claimed... 

Dopamine agonists are useful as initial therapy, as they can delay the need to start levodopa and can decrease the risk of developing motor fluctuations by two- to threefold during the first 4 to 5 years of treatment. After a few years, dopamine agonists inadequately control the patient s symptoms and levodopa needs to be started. In advanced disease, dopamine agonists can be added to levodopa because they have a longer duration of action, minimize fluctuations in dopamine blood concentrations, decrease off-time, improve wearing-off symptoms, allow a reduction in levodopa dose, and improve ADLs.1-3,16,22,23,26... 

FIGURE 38-1. Primary assessment and initial treatment for complaint of excessive daytime sleepiness. RLS, restless-legs syndrome NPSG, nocturnal polysomnography OSA, obstructive sleep apnea DA, dopamine agonist MSLT, multiple sleep latency test BZDRA, benzodiazepine receptor agonist SNRI, serotonin and norepinephrine reuptake inhibitor TCA, tricyclic antidepressant CPAP, continuous positive airway pressure. 

Dopamine agonists are the first-line treatment of choice for all patients with hyperprolactinemia transsphenoidal surgery and radiation therapy are reserved for patients who are resistant to or severely intolerant of pharmacologic therapy. 

Women who become pregnant while on a dopamine agonist should discontinue treatment immediately to minimize fetal exposure. Because cabergoline has a long half-life, women who plan to become pregnant should discontinue the drug at least 1 month before planned conception. 

TABLE 43-8. Comparison of Dopamine Agonists for Treatment of Hyperprolactemia47... 

The need to continue dopamine agonists in postmenopausal women must be reassessed because these patients have a higher probability of maintaining normal prolactin levels after treatment is discontinued.52... 

Cory-Slechta DA, McKoy L, Richfield EK. 1997c. Time course and regional basis of Pb-induced changes in MK-801 binding Reversal by chronic treatment with the dopamine agonist apomorphine but not the D1 agonist SKF-82958. J Neurochem 68 2012-2023. 

Pokora MJ, Richfield EK, Cory-Slechta DA. 1996. Preferential vulnerability of nucleus accumbens dopamine binding sites to low-level lead exposure time course of effects and interactions with chronic dopamine agonist treatments. JNeurochem 67 1540-1550. 

New treatment options. A variety of new treatment options are currently under development, and may become available in the near future. Among these are transdermal application of short-acting dopamine agonists. Selective D1-receptor agents, such as dihydrexidine also offer promise. In addition, non-dopaminergic treatments are under development. 

Tamminga, C. A. and Carlsson, A. Partial dopamine agonists and dopaminergic stabilizers, in the treatment of psychosis. Curr. Drug Targets CNS Neurol. Disord. 2 141-147, 2002. 

The pathology of Parkinson s disease is associated with a substantial reduction in neurotransmitters such as dopamine, 5-hydroxytryptamine, GABA, in the brain. Treatment is based on the use of replacement of dopamine or dopamine agonists which relieve the rigidity but do not affect a cure. Currently, there is no laboratory-based diagnostic test for PD and so diagnosis is based on clinical presentation alone. 

Sit SY, Dopamine agonists in the treatment of Parkinson s disease—Past, present and future, Curr Pharm Design 6 1211—1248, 2000. 

Stocchi F, Dopamine agonists in Parkinson s disease—What is their role in early treatment CNS Drugs 10 159—170, 1998. 

Dopamine agonists are also used for the treatment of acromegaly, but although they are much cheaper than somatostatin analogues, they are also less effective, and rarely normalize serum GH concentrations. 

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