Inhibition of dopamine neuron firing by pramipexole, a dopamine D3 receptor-preferring agonist: comparison to other dopamine receptor agonists

Piercey, Montford F.; Hoffmann, William E.; Smith, Martin; Hyslop, Deborah K.

doi:10.1016/0014-2999(96)00454-2

Cited by 160 publications

(122 citation statements)

References 39 publications

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“…Although quinpirole produced a significant inhibition in these experiments, no further effect of SKF38393 was observed. Because a low dose of a D2 agonist acts preferentially on DA neurons (Skirboll et al, 1979;White and Wang, 1986;Piercey et al, 1996a), these results provided the first evidence suggesting that the expression of the D1 effect may not depend on activation of DA autoreceptors. In the second set of experiments, animals were pretreated with high doses of quinpirole.…”

Section: Co-activation Of D2-like Receptors Enables a D1 Agonist To Imentioning

confidence: 74%

“…DA neurons are known to be more sensitive than DA target neurons to systemically administered DA agonists (Skirboll et al, 1979;White and Wang, 1986;Piercey et al, 1996a). The doses of quinpirole used in the above experiments may have been too low to activate D2-like receptors significantly on DA target neurons.…”

Section: Effect Of D1 Agonists On Da Neurons Pretreated With a D2 Agomentioning

confidence: 99%

“…3B). Perhaps because of the development of tachyphalaxis of autoreceptors Piercey et al, 1996a), DA cells remained active after a slow injection of 40 -160 (92 Ϯ 15.8) g/kg. In 9 of 10 cells, subsequent injection of SKF38393 (5 mg/kg, n ϭ 1; 10 mg/kg, n ϭ 6; 20 mg/kg, n ϭ 2) produced a clear further inhibition (Ͼ10% of baseline; Fig.…”

Section: Effect Of D1 Agonists On Da Neurons Pretreated With a D2 Agomentioning

confidence: 99%

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D1–D2 Interaction in Feedback Control of Midbrain Dopamine Neurons

et al. 1997

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Dopamine (DA) D1-like receptors are present in pathways implicated in feedback control of midbrain DA neurons. However, stimulation of these receptors either produces no effect on DA cells, or the effect is inconsistent. It is possible that the expression of a D1 feedback effect requires co-activation of D2-like receptors. To test this hypothesis, we recorded extracellularly the spontaneous activity of nigral DA cells in a low cerveau isolé rat preparation. SKF38393 and dyhydrexidine, two D1 agonists, were administered systemically to animals pretreated with different doses of the D2 agonist quinpirole. Supporting the hypothesis, the two D1 agonists consistently inhibited DA cells in animals given high doses of quinpirole (Ն40 g/kg, i.v.). However, no significant D1 effect was observed in animals pretreated with only low doses (Յ20 g/kg) of quinpirole. Because low doses of D2 agonists preferentially act on DA autoreceptors, and because the D1 inhibition persisted in animals whose DA autoreceptors were blocked by intranigral application of raclopride, our results suggest that the expression of D1 feedback inhibition requires co-activation of D2-like receptors on DA target neurons, instead of DA neurons themselves. These results, together with the finding that chloral hydrate completely blocked the D1 inhibition, may explain why previous studies have failed to show a consistent D1 effect on DA cells and suggest that drugs designed to act specifically on one subtype of DA receptor may, via feedback pathways, influence the action of endogenous DA on other DA receptor subtypes as well.

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Section: Co-activation Of D2-like Receptors Enables a D1 Agonist To Imentioning

confidence: 74%

Section: Effect Of D1 Agonists On Da Neurons Pretreated With a D2 Agomentioning

confidence: 99%

Section: Effect Of D1 Agonists On Da Neurons Pretreated With a D2 Agomentioning

confidence: 99%

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D1–D2 Interaction in Feedback Control of Midbrain Dopamine Neurons

et al. 1997

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“…It has very low affinity for D1, moderate binding to ␣ 2 adrenoceptor, and low affinity for ␣ 1 and ␣ 1B adrenoceptors, acetylcholine receptors, and serotonin receptors. 43 Pramipexole causes complete suppression of firing of neurons in the substantia nigra pars compacta and the ventral tegmental area. This is an autoreceptor effect, which results in a decrease in DA metabolism.…”

Section: Dopamine Agonistsmentioning

confidence: 99%

“…The affinity of this drug is similar to that of DA for the D2 subfamily, D3 Ͼ D2 Ͼ D4. 43 In addition to binding to postsynaptic receptors, ropinirole stimulates presynaptic D2 autoreceptors causing a dose-dependent decrease in whole-brain levels of the two major metabolites of DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), and stops the firing rate of substantia nigral cells in animal models, 48 making it a full agonist.…”

Section: Dopamine Agonistsmentioning

confidence: 99%

Current Status of Symptomatic Medical Therapy in Parkinson’s Disease

Factor

2008

Neurotherapeutics

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Summary: Symptomatic medical therapies for Parkinson's disease (PD) have been disease modifying and have led to improvement in daily function, quality of life, and survival. For 40 years, these therapies have been primarily dopaminergic, and currently include the dopamine (DA) precursor levodopa (LD), DA agonists, catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors. The roles of all these classes of agents have evolved, with significant changes occurring since the early 2000s. This article reviews the current literature for each of these classes of drugs, with a focus on efficacy and place in the therapeutic scheme. Levodopa is no longer considered to be toxic and, thus, its early use is not only appropriate but recommended.Ergot agonists are no longer in use, and new agents administered in patch form or subcutaneous injections have been approved. The COMT inhibitor tolcapone, with its significant efficacy, has been reintroduced, and two new MAO inhibitors have been approved. Selected safety issues are discussed, including the incidence of melanoma in relation to LD; pathological gambling and DA agonists; hepatic toxicity of tolcapone; and the tyramine or so-called cheese reaction with MAO B inhibitors. The article closes with a discussion of future directions and new drugs under development.

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