Dopamine agonist

Last updated
Dopamine agonist
Drug class
Dopamine.svg
The skeletal structure of dopamine
Class identifiers
Use Parkinson's disease, hyperprolactinemia, restless legs syndrome
ATC code N04BC
Biological target Dopamine receptors
External links
MeSH D010300
Legal status
In Wikidata

A dopamine agonist(DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. [1] Dopamine agonists are primarily used in the treatment of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. [2] They are also used off-label in the treatment of clinical depression. The use of dopamine agonists is associated with impulse control disorders and dopamine agonist withdrawal syndrome (DAWS). [3]

Contents

Medical uses

Parkinson's disease

Dopamine agonists are mainly used in the treatment of Parkinson's disease. [2]   The cause of Parkinson's is not fully known but genetic factors, for example specific genetic mutations, and environmental triggers have been linked to the disease. [4] In Parkinson's disease dopaminergic neurons that produce the neurotransmitter dopamine in the brain slowly break down and can eventually die. With decreasing levels of dopamine the brain can't function properly and causes abnormal brain activity, which ultimately leads to the symptoms of Parkinson's disease. [5]

There are two fundamental ways of treating Parkinson's disease, either by replacing dopamine or mimicking its effect. [1]

Dopamine agonists act directly on the dopamine receptors and mimic dopamine's effect. [1] Dopamine agonists have two subclasses: ergoline and non-ergoline agonists. Both subclasses target dopamine D2-type receptors. Types of ergoline agonists are cabergoline and bromocriptine and examples of non-ergoline agonists are pramipexole, ropinirole and rotigotine. Ergoline agonists are much less used nowadays because of the risk of cartilage formation in heart valves. [6] [7]

Treatment of depression in Parkinson's patients

Depressive symptoms and disorders are common in patients with Parkinson's disease and can affect their quality of life. [8] Increased anxiety can accentuate the symptoms of Parkinson's and is therefore essential to treat. Instead of conventional antidepressant medication in treating depression, treatment with dopamine agonists has been suggested. [9] It is mainly thought that dopamine agonists help with treating depressive symptoms and disorders by alleviating motor complications, which is one of the main symptoms of Parkinson's disease.  Although preliminary evidence of clinical trials has shown interesting results, further research odds crucial to establish the anti-depressive effects of dopamine agonists in treating depressive symptoms and disorders in those with Parkinson's. [8]

Hyperprolactinemia

Dopamine is a prolactin-inhibiting factor (PIFs) since it lowers the prolactin-releasing factors (PRFs) synthesis and secretion through D2-like receptors. [10] That is why dopamine agonists are the first-line treatment in hyperprolactinemia. [11] Ergoline-derived agents, bromocriptine and cabergoline are mostly used in treatment. Research shows that these agents reduce the size of prolactinomas by suppressing the hypersecretion of prolactin resulting in normal gonadal function. [12]

Restless leg syndrome

Numerous clinical trials have been performed to assess the use of dopamine agonists for the treatment of restless leg syndrome (RLS). RLS is identified by the strong urge to move and is a dopamine-dependent disorder. RLS symptoms decrease with the use of drugs that stimulate dopamine receptors and increase dopamine levels, such as dopamine agonists. [13]

Adverse effects

Side effects

Dopamine agonists are mainly used to treat Parkinson's disease, but are also used to treat hyperprolactinemia and restless legs syndrome. [14] The side effects are mainly recorded in treatment for Parkinson's disease where dopamine agonists are commonly used, especially as first-line treatment with levodopa. [15]

Dopamine agonists are divided into two subgroups or drug classes, first-generation and newer agents. Ergoline derived agonists are the first generation and are not used as much as the newer generation the non-ergoline derived agonists. Ergoline derived agonists are said to be "dirtier" drugs because of their interaction with other receptors than dopamine receptors, therefore they cause more side effects. Ergoline derived agonists are for example bromocriptine, cabergoline, pergolide and lisuride. Non-ergoline agonists are pramipexole, ropinirole, rotigotine, piribedil and apomorphine. [1]

The most common adverse effects are constipation, nausea and headaches. Other serious side effects are hallucinations, peripheral edema, gastrointestinal ulcers, pulmonary fibrosis and psychosis. [1] [15]

Dopamine agonists have been linked to cardiac problems. Side effects such as hypotension, myocardial infarction, congestive heart failure, cardiac fibrosis, pericardial effusion and tachycardia. [1] A high risk for valvular heart disease has been established in association with ergot-derived agonists especially in elderly patients with hypertension. [16]

Somnolence and sleep attacks have been reported as an adverse effect that happen to almost 30% of patients using dopamine agonists. Daytime sleepiness, insomnia and other sleep disturbances have been reported as well. [1] [17] [18]

Impulse control disorder that is described as gambling, hypersexuality, compulsive shopping and binge eating is one serious adverse effect of dopamine agonists. [14]

After long-term use of dopamine agonist a withdrawal syndrome may occur when discontinuing or during dose reduction. The following side effects are possible: anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalised pain, and drug cravings. For some individuals, these withdrawal symptoms are short-lived and make a full recovery, for others a protracted withdrawal syndrome may occur with withdrawal symptoms persisting for months or years. [19]

Interactions

Dopamine agonists interact with a number of drugs but there is little evidence that they interact with other Parkinson's drugs. In most cases there is no reason not to co-administer Parkinson's drugs, but there have been indications that the concurrent use of dopamine agonists with L-DOPA can cause psychosis, and therefore in these cases it is recommended that either the dopamine agonist(s) be discontinued or the dose of L-DOPA reduced. Since ergot-dopamine agonist have antihypertensive qualities it is wise to monitor blood pressure when using dopamine agonists with antihypertensive drugs to ensure that the patient does not get hypotension. That includes the drug sildenafil which is commonly used to treat erectile dysfunction but also used for pulmonary hypertension. [20]

There is evidence that suggests that since ergot dopamine agonists are metabolized by CYP3A4 enzyme concentration rises with the use of CYP3A4 inhibitors. For example, in one study bromocriptine was given with a CYP3A4 inhibitor and the AUC (area under the curve) increased 268%. Ropinirole is a non-ergot derived dopamine agonist and concomitant use with a CYP1A2 inhibitor can result in a higher concentration of ropinirole. When discontinuing the CYP1A2 inhibitor, if using both drugs, there is a change that a dose adjustment for ropinirole is needed. There is also evidence the dopamine agonists inhibit various CYP enzymes and therefore they may inhibit the metabolism of certain drugs. [15]

Pharmacology

Ergoline class

Pharmacokinetics of Bromocriptine

Absorption of bromocriptine oral dose is approximately 28%; however, only 6% reaches the systemic circulation unchanged, due to a substantial first-pass effect. Bromocriptine reaches mean peak plasma levels after about 1–1.5 hours after a single oral dose. The drug has high protein binding, ranging from 90-96% bound to serum albumin. Bromocriptine is metabolized by CYP3A4 and excreted primarily in the feces via biliary secretion. Metabolites and parent drugs are mostly excreted via the liver, but also 6% via the kidney. It has a half-life of 2–8 hours. [1]

Pharmacokinetics of Pergolide

Pergolide has a long half-life of about 27 hours and reaches a mean peak plasma level in about 2–3 hours after a single oral dose. The protein binding is 90% and the drug is mainly metabolized in the liver by CYP3A4 and CYP2D6. The major route of excretion is through the kidneys. [1] [21]

Drug

Maintenance

Half-life

Protein bindingPeak plasmaMetabolismExcretion
Bromocriptine

Oral, 2.5–40 mg/day

2–8 hours90-96%1-1,5 hours

Hepatic, via CYP3A4, 93% first-pass metabolism

Bile, 94-98%

Renal, 2-6%

Pergolide

Oral, 0.05 mg/day Usual response up to 0.1 mg per day

27 hours90%2–3 hoursExtensively hepaticRenal, 50%

Fecal 50%

Non-Ergoline class

Pharmacokinetics of Pramipexole

Pramipexole reaches maximum plasma concentration 1–3 hours post-dose. It is about 15% bound to plasma proteins and the metabolism is minimal. Pramipexole has a long half-life, around 27 hours. The drug is mostly excreted in the urine, around 90%, but also in feces. [1]

Pharmacokinetics of Ropinirole

Ropinirole is rapidly absorbed after a single oral dose, reaching plasma concentration in approximately 1–2 hours. The half-life is around 5–6 hours. Ropinirole is heavily metabolized by the liver and in vitro studies show that the enzyme involved in the metabolism of ropinirole is CYP1A2. [22]

Pharmacokinetics of Rotigotine

Since rotigotine is a transdermal patch it provides continuous drug delivery over 24 hours. [23] It has a half-life of 3 hours and the protein binding is around 92% in vitro and 89.5% in vivo. Rotigotine is extensively and rapidly metabolized in the liver and by the CYP enzymes. The drug is mostly excreted in urine (71%), but also in feces (23%). [1]

Drug

Maintenance

Half-life

Protein bindingPeak plasmaMetabolismExcretion
Pramipexole

Oral, 0.125 mg 3x/day (IR) Oral, 0.375 mg/day (ER)

8–12 hours15%1–3 hoursMinimal < 10%Urine 90%

Fecal 2%

Ropinirole

Oral, 0.25 mg 3x/day (IR) Oral, 2 mg/day (ER)

5–6 hours10-40%1–2 hoursHepatic, via P450 CYP1A2 — can increase ↑ INRRenal > 88%
Rotigotine

Transdermal, 2 – 4 mg/day

3 hours

92%

24 hoursHepatic (CYP-mediated).Urine 71%

Fecal 23%

Mechanism of action

The dopamine receptors are 7-transmembrane domains and are members of the G protein-coupled receptors (GPCR) superfamily. Dopamine receptors have five subtypes, D1 through D5, the subtypes can be divided into two subclasses due to their mechanism of action on adenylate cyclase enzyme, D1-like receptors (D1 and D5) and D2-like receptors (D2, D3 and D4). D1-like receptors are primarily coupled to Gαs/olf proteins and activates adenylate cyclase which increases intracellular levels of cAMP, they also activate the Gβγ complex and the N-type Ca2+ channel. D2-like receptors decrease intracellular levels of the second messenger cAMP by inhibiting adenylate cyclase. [24] [25]

Bromocriptine

Bromocriptine is an ergot derivative, semi-synthetic. Bromocriptine is a D2 receptor agonist and D1 receptor antagonist with a binding affinity to D2 receptors of anterior pituitary cells, exclusively on lactotrophs. Bromocriptine stimulates Na+, K+-ATPase activity and/or cytosolic Ca2+ elevation and therefore reduction of prolactin which leads to no production of cAMP.

Pramipexole

Pramipexole is a highly active non-ergot D2-like receptor agonist with a higher binding affinity to D3 receptors rather than D2 or D4 receptors. The mechanism of action of pramipexole is mostly unknown, it is thought to be involved in the activation of dopamine receptors in the area of the brain where the striatum and the substantia nigra is located. This stimulation of dopamine receptors in the striatum may lead to the better movement performance. [26]

Structure–activity relationship

When dealing with agonists it can be extremely complex to confirm relationships between structure and biological activity. Agonists generate responses from living tissues. Therefore, their activity depends both on their efficacy to activate receptors and their affinity to bind to receptors. [27]

Crossing the blood brain barrier

Many molecules are unable to cross the blood brain barrier (BBB). Molecules must be small, non-polar and lipophilic to cross over. If compounds do not possess these qualities they must have a specific transporter that can transport them over the BBB. [28] Dopamine cannot diffuse across the BBB because of the catechol group, it is too polar and therefore unable to enter the brain. The catechol group is a dihydroxy benzene ring.

The synthesis of dopamine consists of three stages. The synthesis process starts with an amino acid, called L-Tyrosine. In the second stage Levodopa (L-dopa) is formed by adding a phenol group to the benzene ring of L-Tyrosine. The formation of L-dopa from L-tyrosine is catalyzed by the enzyme tyrosine hydroxylase. The third stage is the formation of dopamine by removing the carboxylic acid group from L-dopa, catalysed by the enzyme dopa decarboxylase. [29]

Levodopa is also too polar to cross the blood brain barrier but it happens to be an amino acid so it has a specialized transporter called L-type amino acid transporter or LAT-1 that helps it diffuse through the barrier. [30]

Dopamine

When dopamine interacts with ATP, which is a component of some dopamine receptors, it has a significant preference for a trans-conformation of the dopamine molecule. The dopamine-ATP complex is stabilised by hydrogen bonding between catechol hydroxyls and purine nitrogens and by electrostatic interactions between the protonated ammonium group of dopamine and a negative phosphate group. Two conformers of dopamine have been identified as alpha- and beta-conformers in which the catechol ring is coplanar with the plane of the ethylamine side chain. They are substantial in agonist-receptor interactions. [31]

Ergoline derivatives

Central dopaminergic agonist properties of semisynthetic ergoline derivatives lergotrile, pergolide, bromocriptine and lisuride have been established. Some studies suggest that ergot alkaloids have the properties of mixed agonist-antagonist with regards to certain presynaptic and postsynaptic receptors. N-n-Propyl groups (chemical formula: –CH2CH2CH3) frequently enhance dopamine agonist effects in the ergoline derivatives.

Bromocriptine Bromocriptine.svg
Bromocriptine

The (+)-enantiomer displays notably diminished activity whereas the (-)-enantiomer possess potent dopamine agonist properties. [31]

Bromocriptine

Bromocriptine has an ergot alkaloid structure. Ergot alkaloids are divided into 2 groups; amino acid ergot alkaloids and amine ergot alkaloids, bromocriptine is part of the former group. [32] It contains a bromine halogen on the ergot structure which increases the affinity for the D2-receptor but often reduces the efficacy. The similarity between the dopamine structure and the ergoline ring in bromocriptine is likely the cause for its action on the dopamine receptors. [33] It has shown to have equal affinity for D2- and D3-receptor and much lower affinity for D1-receptor. [34]

Apomorphine Apomorphine.svg
Apomorphine

Non-ergoline derivatives

Non-ergoline dopamine receptor agonists have higher binding affinity to dopamine D3-receptors than dopamine D2-receptors. This binding affinity is related to D2 and D3 receptor homology, the homology between them has a high degree of sequence and is closest in their transmembrane domains, were they share around 75% of the amino acid. [35]

Rotigotine Rotigotine.svg
Rotigotine

Apomorphine

Apomorphine has a catechol element and belongs to a class called β-phenylethylamines and its main components are similar to the dopamine structure. The effect that apomorphine has on the dopamine receptors can also be linked to the similarities between its structure and dopamine. [36] It is a chiral molecule and thus can be acquired in both the R and S form, the R form is the one that is used in therapy. When apomorphine interacts with the dopamine receptor, or the ATP on the receptor, the catechol and nitrogen are important to stabilize the structure with hydrogen bonding. The position of the hydroxyl groups is also important and monohydroxy derivatives have been found to be less potent than the dihydroxy groups. There are a number of stability concerns with apomorphine such as oxidation and racemization. [37]

Rotigotine

Rotigotine is a phenolic amine and thus has poor oral bioavailability and fast clearance from the body. Therefore, it has been formulated as a transdermal patch, first and foremost to prevent first pass metabolism in the liver. [38]

Members

Examples of dopamine agonists include:

Partial agonist

Agonists of full/unknown efficacy

Some, such as fenoldopam, are selective for dopamine receptor D1. [43]

There are two classes of drugs that act as indirect agonists of dopamine receptors: dopamine reuptake inhibitors and dopamine releasing agents. These are not considered dopamine agonists, since they have no specific agonist activity at dopamine receptors, but they are nonetheless related. Indirect agonists are prescribed for a wider range of conditions than standard dopamine agonists.

The most commonly prescribed indirect agonists of dopamine receptors include:

Other examples include:

History

Since the late 1960 Levodopa (L-DOPA) has been used to treat Parkinson's disease but there has always been a debate whether the treatment is worth the side effects. [45] Around 1970 clinicians started using the dopamine agonist apomorphine alongside L-DOPA to minimize the side effects caused by L-DOPA, the dopamine agonists bind to the dopamine receptor in the absence of dopamine. Apomorphine had limited use since it had considerable side effects and difficulty with administration. In 1974 bromocriptine was use widely after clinicians discovered its benefits in treating Parkinsons. [46] When using the two drug classes together there is a possibility to reduce the amount of L-DOPA by 20-30% and thus keeping the fluctuating motor responses to a minimum. [7] Dopamine agonists are often used in younger people as monotherapy and as initial therapy instead of L-DOPA. [7] Although it is important to know that there is a correlation between the two drugs, if l-DOPA doesn't work dopamine agonists are also ineffective. [1]

The early dopamine agonists, such as bromocriptine, were ergot derived and activated the D2-receptor. [7] They induced major side effects such as fibrosis of cardiac valves. It is considered that the reason they induced such side effects is that they activate many types of receptors. [1]

Due to the major adverse effects of ergot-derived dopamine agonists, they are generally not used in modern medicine and have mostly been abandoned in favor of non-ergot agonists such as pramipexole, ropinirole and rotigotine. They do not induce as serious side effects although common side effects are nausea, edema and hypotension. Patients have also shown impaired impulse control such as overspending, hypersexuality and gambling. [47]

See also

Related Research Articles

<span class="mw-page-title-main">Ergoline</span> Chemical compound

Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of these are implicated in the condition ergotism, which can take a convulsive form or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives.

<span class="mw-page-title-main">Bromocriptine</span> Organic Chemical Compound

Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes.

<span class="mw-page-title-main">Pergolide</span> Dopamine agonist medication

Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced dopamine activity in the substantia nigra of the brain. Pergolide acts on many of the same receptors as dopamine to increase receptor activity.

<span class="mw-page-title-main">Cabergoline</span> Chemical compound

Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being opioids, which enhance dopamine release indirectly in the reward pathways, and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.

<span class="mw-page-title-main">Ropinirole</span> Dopamine agonist medication

Ropinirole, sold under the brand name Requip among others, is a medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). It is taken by mouth.

<span class="mw-page-title-main">Apomorphine</span> Chemical compound

Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non-selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antagonist of 5-HT2 and α-adrenergic receptors with high affinity. The compound is historically a morphine decomposition product made by boiling morphine with concentrated acid, hence the -morphine suffix. Contrary to its name, apomorphine does not actually contain morphine or its skeleton, nor does it bind to opioid receptors. The apo- prefix relates to it being a morphine derivative ("[comes] from morphine").

<span class="mw-page-title-main">Pramipexole</span> Dopamine agonist medication

Pramipexole, sold under the brand Mirapex among others, is medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In Parkinson's disease it may be used alone or together with levodopa. It is taken by mouth. Pramipexole is a dopamine agonist of the non-ergoline class.

<span class="mw-page-title-main">Lisuride</span> Chemical compound

Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.

<span class="mw-page-title-main">Rotigotine</span> Dopamine agonist medication

Rotigotine, sold under the brand name Neupro among others, is a dopamine agonist of the non-ergoline class of medications indicated for the treatment of Parkinson's disease and restless legs syndrome. It is formulated as a once-daily transdermal patch which provides a slow and constant supply of the drug over the course of 24 hours.

<span class="mw-page-title-main">Nicergoline</span> Chemical compound

Nicergoline, sold under the brand name Sermion among others, is an ergot derivative used to treat senile dementia and other disorders with vascular origins. Internationally it has been used for frontotemporal dementia as well as early onset in Lewy body dementia and Parkinson's dementia. It decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells. It has similar vasoactive properties in other areas of the body, particularly the lungs. Unlike many other ergolines, such as ergotamine, nicergoline is not associated with cardiac fibrosis.

<span class="mw-page-title-main">Piribedil</span> Drug used in the management of Parkinsons disease

Piribedil (trade names Pronoran, Trivastal Retard, Trastal, Trivastan, Clarium and others) is an antiparkinsonian agent and piperazine derivative which acts as a D2 and D3 receptor agonist. It also has α2-adrenergic antagonist properties.

<span class="mw-page-title-main">Dihydroergocryptine</span> Chemical compound

Dihydroergocryptine (DHEC), sold under the brand names Almirid and Cripar among others, is a dopamine agonist of the ergoline group that is used as an antiparkinson agent in the treatment of Parkinson's disease. It is taken by mouth.

Dopamine receptor D<sub>2</sub> Main receptor for most antipsychotic drugs

Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined.

Dopamine receptor D<sub>1</sub> Protein-coding gene in humans

Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family — receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.

Dopamine receptor D<sub>3</sub> Subtype of Dopamine Receptor

Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.

<span class="mw-page-title-main">Dopamine dysregulation syndrome</span> Medical condition

Dopamine dysregulation syndrome (DDS) is a dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time. It typically occurs in people with Parkinson's disease (PD) who have taken dopamine agonist medications for an extended period of time. It is characterized by problems such as addiction to medication, gambling, or sexual behavior.

Levodopa-induced dyskinesia (LID) is a form of dyskinesia associated with levodopa (l-DOPA), used to treat Parkinson's disease. It often involves hyperkinetic movements, including chorea, dystonia, and athetosis.

<span class="mw-page-title-main">CY-208,243</span> Chemical compound

CY-208,243 is a drug which acts as a dopamine agonist selective for the D1 subtype. Unlike most D1-selective agonists, it shows efficacy in animal models of Parkinson's disease.

<span class="mw-page-title-main">Prolactin modulator</span> Drug class

A prolactin modulator is a drug which affects the hypothalamic–pituitary–prolactin axis by modulating the secretion of the pituitary hormone prolactin from the anterior pituitary gland. Prolactin inhibitors suppress and prolactin releasers induce the secretion of prolactin, respectively.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 Borovac JA (March 2016). "Side effects of a dopamine agonist therapy for Parkinson's disease: a mini-review of clinical pharmacology". The Yale Journal of Biology and Medicine. 89 (1): 37–47. PMC   4797835 . PMID   27505015.
  2. 1 2 Silva MA, Mattern C, Häcker R, Tomaz C, Huston JP, Schwarting RK (December 1997). "Increased neostriatal dopamine activity after intraperitoneal or intranasal administration of L-DOPA: on the role of benserazide pretreatment". Synapse. 27 (4): 294–302. doi:10.1002/(sici)1098-2396(199712)27:4<294::aid-syn3>3.3.co;2-z. PMID   9372552.
  3. ↑ Elliott, Carl. "The Degradation Drug". The American Scholar. Retrieved 15 September 2022.
  4. ↑ Howes OD, McCutcheon R, Owen MJ, Murray RM (January 2017). "The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia". Biological Psychiatry. 81 (1): 9–20. doi:10.1016/j.biopsych.2016.07.014. PMC   5675052 . PMID   27720198.
  5. ↑ DeMaagd G, Philip A (August 2015). "Parkinson's Disease and Its Management: Part 1: Disease Entity, Risk Factors, Pathophysiology, Clinical Presentation, and Diagnosis". P & T. 40 (8): 504–32. PMC   4517533 . PMID   26236139.
  6. ↑ Antonini, Angelo; Poewe, Werner (2007). "Fibrotic heart-valve reactions to dopamine-agonist treatment in Parkinson's disease". The Lancet Neurology. 6 (9). Elsevier BV: 826–829. doi:10.1016/s1474-4422(07)70218-1. ISSN   1474-4422. PMID   17706566. S2CID   39526238.
  7. 1 2 3 4 Brooks DJ (June 2000). "Dopamine agonists: their role in the treatment of Parkinson's disease". Journal of Neurology, Neurosurgery, and Psychiatry. 68 (6): 685–9. doi:10.1136/jnnp.68.6.685. PMC   1736955 . PMID   10811688.
  8. 1 2 Barone P (March 2011). "Treatment of depressive symptoms in Parkinson's disease". European Journal of Neurology. 18 (Suppl 1): 11–5. doi:10.1111/j.1468-1331.2010.03325.x. PMID   21255198. S2CID   5827695.
  9. ↑ Leentjens AF (February 2011). "The role of dopamine agonists in the treatment of depression in patients with Parkinson's disease: a systematic review". Drugs. 71 (3): 273–86. doi:10.2165/11585380-000000000-00000. PMID   21319866. S2CID   38988462.
  10. ↑ Mancini, Tatiana; Casanueva, Felipe F.; Giustina, Andrea (2008-03-01). "Hyperprolactinemia and Prolactinomas". Endocrinology and Metabolism Clinics of North America. Pituitary Disorders. 37 (1): 67–99. doi:10.1016/j.ecl.2007.10.013. ISSN   0889-8529. PMID   18226731.
  11. ↑ Verhelst, Johan; Abs, Roger; Maiter, Dominique; van den Bruel, Annick; Vandeweghe, Mark; Velkeniers, Brigitte; Mockel, Jean; Lamberigts, Gerard; Petrossians, Patrick; Coremans, Peter; Mahler, Charles (1999-07-01). "Cabergoline in the Treatment of Hyperprolactinemia: A Study in 455 Patients". The Journal of Clinical Endocrinology & Metabolism. 84 (7): 2518–2522. doi: 10.1210/jcem.84.7.5810 . ISSN   0021-972X. PMID   10404830.
  12. ↑ Webster, Jonathan; Piscitelli, Gabriella; Polli, Anna; Ferrari, Carlo I.; Ismail, Ikram; Scanlon, Maurice F. (1994-10-06). "A Comparison of Cabergoline and Bromocriptine in the Treatment of Hyperprolactinemic Amenorrhea". New England Journal of Medicine. 331 (14): 904–909. doi: 10.1056/NEJM199410063311403 . ISSN   0028-4793. PMID   7915824.
  13. ↑ Zintzaras E, Kitsios GD, Papathanasiou AA, Konitsiotis S, Miligkos M, Rodopoulou P, Hadjigeorgiou GM (February 2010). "Randomized trials of dopamine agonists in restless legs syndrome: a systematic review, quality assessment, and meta-analysis". Clinical Therapeutics. 32 (2): 221–37. doi:10.1016/j.clinthera.2010.01.028. PMID   20206780.
  14. 1 2 Moore TJ, Glenmullen J, Mattison DR (December 2014). "Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs". JAMA Internal Medicine. 174 (12): 1930–3. doi:10.1001/jamainternmed.2014.5262. PMID   25329919.
  15. 1 2 3 Kvernmo T, Härtter S, Burger E (August 2006). "A review of the receptor-binding and pharmacokinetic properties of dopamine agonists". Clinical Therapeutics. 28 (8): 1065–1078. doi:10.1016/j.clinthera.2006.08.004. PMID   16982285.
  16. ↑ Peralta C, Wolf E, Alber H, Seppi K, Müller S, Bösch S, et al. (August 2006). "Valvular heart disease in Parkinson's disease vs. controls: An echocardiographic study". Movement Disorders. 21 (8): 1109–13. doi:10.1002/mds.20887. PMID   16622856. S2CID   26909111.
  17. ↑ Wood LD (April 2010). "Clinical review and treatment of select adverse effects of dopamine receptor agonists in Parkinson's disease". Drugs & Aging. 27 (4): 295–310. doi:10.2165/11318330-000000000-00000. PMID   20359261. S2CID   21096318.
  18. ↑ Tholfsen LK, Larsen JP, Schulz J, Tysnes OB, Gjerstad MD (July 2015). "Development of excessive daytime sleepiness in early Parkinson disease". Neurology. 85 (2): 162–8. doi:10.1212/WNL.0000000000001737. PMID   26085603. S2CID   17598980.
  19. ↑ Nirenberg MJ (August 2013). "Dopamine agonist withdrawal syndrome: implications for patient care". Drugs & Aging. 30 (8): 587–92. doi:10.1007/s40266-013-0090-z. PMID   23686524. S2CID   207489653.
  20. ↑ Jost WH, Brück C (October 2002). "Drug interactions in the treatment of Parkinson's disease". Journal of Neurology. 249 (Suppl 3): III/24–9. doi:10.1007/s00415-002-1305-0. PMID   12522568. S2CID   39469174.
  21. ↑ Blin O (December 2003). "The pharmacokinetics of pergolide in Parkinson's disease". Current Opinion in Neurology. 16 (Suppl 1): S9-12. doi:10.1097/00019052-200312001-00003. PMID   15180132. S2CID   1734931.
  22. ↑ Kaye CM, Nicholls B (October 2000). "Clinical pharmacokinetics of ropinirole". Clinical Pharmacokinetics. 39 (4): 243–54. doi:10.2165/00003088-200039040-00001. PMID   11069211. S2CID   9977681.
  23. ↑ Elshoff JP, Cawello W, Andreas JO, Mathy FX, Braun M (April 2015). "An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson's disease and restless legs syndrome". Drugs. 75 (5): 487–501. doi:10.1007/s40265-015-0377-y. PMC   4382528 . PMID   25795100.
  24. ↑ Peterson SM, Urs N, Caron MG (2012-01-01), Robertson D, Biaggioni I, Burnstock G, Low PA (eds.), "Chapter 13 - Dopamine Receptors", Primer on the Autonomic Nervous System (Third Edition), Academic Press, pp. 67–70, doi:10.1016/B978-0-12-386525-0.00013-5, ISBN   9780123865250
  25. ↑ "Dopamine D1-Like Receptor Family Signaling Pathways". www.rndsystems.com. Retrieved 2019-10-08.
  26. ↑ Weng JJ, Wang LH, Zhu H, Xu WR, Wei YM, Wang ZY, et al. (2019). "3 partial agonist pramipexole on neuroleptic-induced extrapyramidal symptoms and symptoms of schizophrenia: a stage-1 open-label pilot study". Neuropsychiatric Disease and Treatment. 15: 2195–2203. doi: 10.2147/NDT.S205933 . PMC   6689661 . PMID   31496702.
  27. ↑ Ravikumar K, Sridhar B (May 2006). "Ropinirole hydrochloride, a dopamine agonist". Acta Crystallographica Section C. 62 (Pt 5): o265-7. doi:10.1107/S0108270106010535. PMID   16679599.
  28. ↑ Banks WA (June 2009). "Characteristics of compounds that cross the blood-brain barrier". BMC Neurology. 9 (Suppl 1): S3. doi: 10.1186/1471-2377-9-S1-S3 . PMC   2697631 . PMID   19534732.
  29. ↑ Best JA, Nijhout HF, Reed MC (September 2009). "Homeostatic mechanisms in dopamine synthesis and release: a mathematical model". Theoretical Biology & Medical Modelling. 6 (1): 21. doi: 10.1186/1742-4682-6-21 . PMC   2755466 . PMID   19740446.
  30. ↑ Kageyama T, Nakamura M, Matsuo A, Yamasaki Y, Takakura Y, Hashida M, et al. (October 2000). "The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier". Brain Research. 879 (1–2): 115–21. doi:10.1016/s0006-8993(00)02758-x. PMID   11011012. S2CID   33605179.
  31. 1 2 Cannon JG (1983). "Structure-activity relationships of dopamine agonists". Annual Review of Pharmacology and Toxicology. 23: 103–29. doi:10.1146/annurev.pa.23.040183.000535. PMID   6347047.
  32. ↑ Oda T, Kume T, Izumi Y, Takada-Takatori Y, Niidome T, Akaike A (November 2008). "Bromocriptine, a dopamine D(2) receptor agonist with the structure of the amino acid ergot alkaloids, induces neurite outgrowth in PC12 cells". European Journal of Pharmacology. 598 (1–3): 27–31. doi:10.1016/j.ejphar.2008.09.015. PMID   18835264.
  33. ↑ Markstein R, Seiler MP, Jaton A, Briner U (March 1992). "Structure activity relationship and therapeutic uses of dopaminergic ergots". Neurochemistry International. Satellite Meeting of the XIth International Congress of Pharmacology. 20 (Suppl): 211S–214S. doi:10.1016/0197-0186(92)90241-I. PMID   1365428. S2CID   27230073.
  34. ↑ Perachon S, Schwartz JC, Sokoloff P (February 1999). "Functional potencies of new antiparkinsonian drugs at recombinant human dopamine D1, D2 and D3 receptors". European Journal of Pharmacology. 366 (2–3): 293–300. doi:10.1016/S0014-2999(98)00896-6. PMID   10082211.
  35. ↑ Platania CB, Salomone S, Leggio GM, Drago F, Bucolo C (2012-09-06). "Homology modeling of dopamine D2 and D3 receptors: molecular dynamics refinement and docking evaluation". PLOS ONE. 7 (9): e44316. Bibcode:2012PLoSO...744316P. doi: 10.1371/journal.pone.0044316 . PMC   3435408 . PMID   22970199.
  36. ↑ Borkar N, Mu H, Holm R (2018-11-01). "Challenges and trends in apomorphine drug delivery systems for the treatment of Parkinson's disease". Asian Journal of Pharmaceutical Sciences. Formulation strategies and manufacturing technologies to enhance non-invasive drug delivery. 13 (6): 507–517. doi: 10.1016/j.ajps.2017.11.004 . ISSN   1818-0876. PMC   7032113 . PMID   32104425.
  37. ↑ Subramony JA (2006). "Apomorphine in dopaminergic therapy". Molecular Pharmaceutics. 3 (4): 380–5. doi:10.1021/mp060012c. PMID   16889431.
  38. ↑ Risgaard R, Jensen M, Jørgensen M, Bang-Andersen B, Christoffersen CT, Jensen KG, et al. (January 2014). "Synthesis and SAR study of a novel series of dopamine receptor agonists". Bioorganic & Medicinal Chemistry. 22 (1): 381–92. doi:10.1016/j.bmc.2013.11.012. PMID   24296012.
  39. ↑ Seeman P, Guan HC, Hirbec H (2009). "Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil". Synapse. 63 (8): 698–704. doi:10.1002/syn.20647. PMID   19391150. S2CID   17758902.
  40. ↑ Conroy JL, Free RB, Sibley DR (April 2015). "Identification of G protein-biased agonists that fail to recruit β-arrestin or promote internalization of the D1 dopamine receptor". ACS Chemical Neuroscience. 6 (4): 681–92. doi:10.1021/acschemneuro.5b00020. PMC   5234767 . PMID   25660762.
  41. ↑ FDA Announces Voluntary Withdrawal of Pergolide Products
  42. ↑ Matera C, Quadri M, Pelucchi S, De Amici M, Dallanoce C (April 17, 2014). "A convenient synthesis of 4-(2-hydroxyethyl)indolin-2-one, a useful intermediate for the preparation of both dopamine receptor agonists and protein kinase inhibitors". Monatshefte für Chemie . 145 (7): 1139–1144. doi:10.1007/s00706-014-1211-z. hdl: 2434/236639 . S2CID   84265684.
  43. ↑ Ng SS, Pang CC (March 2000). "In vivo venodilator action of fenoldopam, a dopamine D(1)-receptor agonist". British Journal of Pharmacology. 129 (5): 853–8. doi:10.1038/sj.bjp.0703119. PMC   1571905 . PMID   10696081.
  44. ↑ Watanabe, H.; Uramoto, H. (June 1986). "Caffeine mimics dopamine receptor agonists without stimulation of dopamine receptors". Neuropharmacology. 25 (6): 577–581. doi:10.1016/0028-3908(86)90208-X.
  45. ↑ Zhang J, Tan LC (2016-04-08). "Revisiting the Medical Management of Parkinson's Disease: Levodopa versus Dopamine Agonist". Current Neuropharmacology. 14 (4): 356–63. doi:10.2174/1570159X14666151208114634. PMC   4876591 . PMID   26644151.
  46. ↑ Tolosa E, Martí MJ, Valldeoriola F, Molinuevo JL (June 1998). "History of levodopa and dopamine agonists in Parkinson's disease treatment". Neurology. 50 (6 Suppl 6): S2–10, discussion S44–8. doi:10.1212/wnl.50.6_suppl_6.s2. PMID   9633679. S2CID   25603106.
  47. ↑ Golan DE, Armstrong EJ, Armstrong AW (2017). Principles of pharmacology - the pathophysiologic basis of drug therapy. Philadelphia: Wolters Kluwer. pp. 214–215. ISBN   9781451191004.

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