Agonists dopamine receptors

DM Mottola, S Laiter, VJ Watts, A Tropsha, SW Wyrick, DE Nichols, P Mailman. Conformational analysis of d dopamine receptor agonists Pharmacophore assessment and receptor mapping. J Med Chem 39 285-296, 1996. 

Parkinsonian patients receiving the dopamine precursor, levodopa or dopamine receptor agonists, such as bromocriptine and apomoiphine may experience nausea and vomiting due to stimulation of dopamine D2 receptors in the CTZ. 

The dopamine receptor agonists, such as pramipexole (Mirapex) and ropinirole (Requip), are used for die treatment of die signs and symptoms of Parkinson s disease... 

There is an increased risk of CNS depression when tiie dopamine receptor agonists are administered witii otiier CNS depressants. When administered witii levodopa, the dopamine receptor agonists increase the effects of levodopa (a lower dosage of levodopa may be required). hi addition, when the dopamine receptor agonists are administered with levodopa, there is an increased risk of hallucinations. When administered witii ciprofloxacin, there is an increased effect of the dopamine receptor agonist. 

The phenotiiiazines may decrease the effectiveness of tiie dopamine receptor agonists. When pramipexole is administered concurrently witii cimetidine, ranitidine, verapamil, and quinidine, there is an increased effect of pramipexole When ropinirole is administered with the estrogens, particularly estradiol, there may be an increased effect of ropinirole... 

I younger adult receiving the antiparkinsonism drugs especially when taking the dopamine receptor agonists The nurse should assess the older adult for sgns of visual, auditory, or tactile hallucinations The incidence of halludnationsappears to increase with age. 

Explain what adverse reaction would be more likely to occur in the older adult prescribed a non-ergot dopamine receptor agonist drug. Describe how you would assess for this adverse reaction. 

Elderly patients prescribed one of the dopamine receptor agonists are monitored closely for which of the following adverse reactions ... 

Hu, XT and Wang, RY (1988) Comparison of effects of Dj and D2 dopamine receptor agonists on neurons in the rat caudate putamen an electrophysiological study. J. Neurosci. 8 4340-4348. 

J.J. and Svendsen, 0. Dopamine receptor agonistic and antagonistic effects of 3-PPP enantiomers. Psvchopharmacoloav 81 199-207, 1983. 

J.L.G. 3-PPP, a new centrally acting dopamine receptor agonist with selectivity for autoreceptors. I ife Sci 28 1225-1238,... 

Pulvirenti L., Koob G. Dopamine receptor agonists, partial agonists and psychostimulant addiction. Trends Pharmacol. Sci. 15 374, 1994. 

Self D., Barnhart W., Lehman D., Nestler E. Opposite modulation of cocaine-seeking behavior by Dl- and D2-like dopamine receptor agonists. Science. 271 1586, 1996. 

A dopamine receptor agonist that is useful in the therapy of Parkinson s disease is... 

The answer is b. (Hardman, pp 282—283J Central dopamine receptors are divided into Dt and D2 receptors. Antipsychotic activity is better correlated to blockade of D2 receptors. Haloperidol, a potent antipsychotic, selectively antagonizes at Dz receptors. Phenothiazine derivatives, such as chlorpromazine, fluphenazine, and promethazine, are not selective for D2 receptors. Bromocriptine, a selective D2 agonist, is useful in the treatment of parkinsonism and hyperprolactinemia. It produces fewer adverse reactions than do nonselective dopamine receptor agonists... 

The answer is d. (Hardman, pp 1371-13720 High prolactin levels in the serum result in amenorrhea, for reasons that are not known. Bromocriptine inhibits prolactin secretion through its dopaminergic action This compound, a semisynthetic ergot derivative, appears to be a dopamine receptor agonist. It is administered orally to the patient and, in most cases, menses occurs after a month of therapy. 

The most important alternatives to levodopa therapy are direct-acting dopamine receptor agonists, such as ropinirole,pramipexole, or pergolide (Fig. 46-5). A number of studies have shown that use of these agents may help to delay the need for use of levodopa/carbidopa. This has... 

FIGURE 46-5 Chemical structures of dopamine receptor agonists. 

Rodriguez, D. F. et al., The dopamine receptor agonist 7-OH-DPAT modulates the acquisition and expression of morphine-induced place preference, Eur. J. Pharmacol., 21 A, 47, 1995. 

In another work, a series of substituted 2-aminoindans was analyzed using MM2-85108. The calculated potential energy surface for rotation around the CH—CH—CH2— N and CH—CH2—N—lp in model compound 70 is presented in Figure 9 and shows 9 minima. These were scrutinized as potential candidates for dopamine receptor agonists, according to several criteria The highest-energy conformation f (Erei = 7.3 kcalmol-1)... 

Apomorphine hydrochloride (44 Apokyn ) Morphine (43) Alkaloid Semi-synthetic NP Plant Parkinson s disease Potent dopamine receptor agonist 403 16... 

Dopamine receptor agonists. Deficient dopaminergic transmission in the striatum can be compensated by ergot derivatives (bromocriptine p. 114], lisu-ride, cabergoline, and pergolide) and nonergot compounds (ropinirole, prami-pexole). These agonists stimulate dopamine receptors (D2, D3, and D sub-types), have lower clinical efficacy than levodopa, and share its main adverse effects. 

Administration of levodopa plus carbidopa (or benserazide) remains the most effective treatment, but does not provide benefit beyond 3-5 y and is followed by gradual loss of symptom control, on-off fluctuations, and development of orobuccofacial and limb dyskinesias. These long-term drawbacks of levodopa therapy may be delayed by early monotherapy with dopamine receptor agonists. Treatment of advanced disease requires the combined administration of antiparkinsonian agents. 

Bromocriptine (11), pergolide (12), cabergoline (13) and lisuride (14) are examples of compounds which have been developed in this way and are now used clinically. The pharmacological differences between the compounds is not very great. All are D2-dopamine receptor agonists, although... 

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