XP-21279

Last updated

XP-21279
XP-21279.svg
Clinical data
Other namesXP21279
Routes of
administration 		Oral [1] [2] [3]
Drug class Dopamine precursor; Dopamine receptor agonist
Identifiers
  • [(2R)-1-[(2S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoyl]oxypropan-2-yl] benzoate
CAS Number
PubChem CID
DrugBank
ChemSpider
ChEMBL
Chemical and physical data
Formula C19H21NO6
Molar mass 359.378 g·mol−1
3D model (JSmol)
  • C[C@H](COC(=O)[C@H](CC1=CC(=C(C=C1)O)O)N)OC(=O)C2=CC=CC=C2
  • InChI=1S/C19H21NO6/c1-12(26-18(23)14-5-3-2-4-6-14)11-25-19(24)15(20)9-13-7-8-16(21)17(22)10-13/h2-8,10,12,15,21-22H,9,11,20H2,1H3/t12-,15+/m1/s1
  • Key:AKUWZLYXAADOTQ-DOMZBBRYSA-N

XP-21279 is a sustained-release levodopa (L-DOPA) prodrug and hence a dopamine precursor and non-selective dopamine receptor agonist which was under development for the treatment of Parkinson's disease. [4] [1] [3] It is taken by mouth. [1] [2] [3]

Contents

Pharmacology

The drug is said to add a five-carbon ester conjugate to levodopa that allows it to be actively transported by high-capacity nutrient transporters throughout the entire gastrointestinal tract. [2] [3] [5] Subsequently, it is rapidly converted into levodopa by carboxylesterases. [2] [3] [5] Levodopa itself can only be transported by a short section of the small intestine and hence XP-21279 allows more time for levodopa to be absorbed, in turn resulting in an increased duration and possibly reduced fluctuations in dopamine levels between levodopa doses. [1] [2] [3]

Clinical studies

As of June 2015, XP-21279 was in phase 2 clinical trials. [4] As of May 2022, there have been no further developmental updates. [4] It was reported in 2018 that development of the drug had been discontinued several years prior. [6] A 2019 review reported that results were conflicting in phase 2 trials and that this likely resulted in the discontinuation of the drug's development. [5]

Chemistry

Many sources do not report the chemical structure of XP-21279, suggesting that its exact structure has not been disclosed. [7] [8] [9] [6] [10] However, one source appears to report its chemical structure. [11]

See also

Related Research Articles

Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of the hands to an uncontrollable movement of the upper body or lower extremities. Discoordination can also occur internally especially with the respiratory muscles and it often goes unrecognized. Dyskinesia is a symptom of several medical disorders that are distinguished by their underlying cause.

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

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

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<span class="mw-page-title-main">Dopamine agonist</span> Compound that activates dopamine receptors

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

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<span class="mw-page-title-main">Mesocarb</span> Stimulant drug

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Catechol-<i>O</i>-methyltransferase inhibitor Medication

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

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<span class="mw-page-title-main">Droxidopa</span> Synthetic amino acid/norepinephrine prodrug

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<span class="mw-page-title-main">Levodopa</span> Dopaminergic medication

Levodopa, also known as L-DOPA and sold under many brand names, is a dopaminergic medication which is used in the treatment of Parkinson's disease and certain other conditions like dopamine-responsive dystonia and restless legs syndrome. The drug is usually used and formulated in combination with a peripherally selective aromatic L-amino acid decarboxylase (AAAD) inhibitor like carbidopa or benserazide. Levodopa is taken by mouth, by inhalation, through an intestinal tube, or by administration into fat.

<span class="mw-page-title-main">Parkinson's disease</span> Long-term neurodegenerative disease

Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease of mainly the central nervous system that affects both the motor and non-motor systems of the body. The symptoms usually emerge slowly, and, as the disease progresses, non-motor symptoms become more common. Usual symptoms include tremors, slowness of movement, rigidity, and difficulty with balance, collectively known as parkinsonism. Parkinson's disease dementia, falls and neuropsychiatric problems such as sleep abnormalities, psychosis, mood swings, or behavioral changes may also arise in advanced stages.

<span class="mw-page-title-main">A-86929</span> Chemical compound

A-86929 is a synthetic compound that acts as a selective dopamine receptor D1 agonist. It was developed as a possible treatment for Parkinson's disease, as well as for other applications such as treatment of cocaine addiction, but while it had reasonable efficacy in humans it also caused dyskinesias and has not been continued. It has mainly been used as its diacetate ester prodrug adrogolide (ABT-431), which has better bioavailability.

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.

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

Foslevodopa is a drug which acts as a prodrug for levodopa, originally invented in the 1980s but not developed for medical use at that time. It has more recently attracted renewed interest due to its improved pharmacokinetics compared to levodopa itself, and is now approved for use in a subcutaneous infusion as a fixed-dose combination with foscarbidopa for the treatment of Parkinson's disease, under the trade name Vyalev.

<span class="mw-page-title-main">Glovadalen</span> D1 receptor positive allosteric modulator under development for Parkinsons disease

Glovadalen (developmental code name UCB-0022) is a dopamine D1 receptor positive allosteric modulator which is under development for the treatment of Parkinson's disease. It has been found to potentiate the capacity of dopamine to activate the D1 receptor by 10-fold in vitro with no actions on other dopamine receptors. As of May 2024, glovadalen is in phase 2 clinical trials for this indication. The drug is under development by UCB Biopharma. It is described as an orally active, centrally penetrant small molecule.

<span class="mw-page-title-main">Neurotransmitter prodrug</span> A prodrug of a neurotransmitter

A neurotransmitter prodrug, or neurotransmitter precursor, is a drug that acts as a prodrug of a neurotransmitter. A variety of neurotransmitter prodrugs have been developed and used in medicine. They can be useful when the neurotransmitter itself is not suitable for use as a pharmaceutical drug owing to unfavorable pharmacokinetic or physicochemical properties, for instance susceptibility to metabolism or lack of blood–brain barrier permeability. Besides their use in medicine, neurotransmitter prodrugs have also been used as recreational drugs in some cases.

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

Mesdopetam (INNTooltip International Nonproprietary Name; developmental code names IRL-790, IPN60170) is a dopamine D2 and D3 receptor antagonist with preference for the D3 receptor which is under development for the treatment of Parkinson's disease, drug-induced dyskinesia, and psychotic disorders. It has been described by its developers as having "psychomotor stabilizing" properties.

Pirepemat is a drug which is under development for the prevention of falls in people with Parkinson's disease and Parkinson's disease dementia. It has been referred to as a "nootrope".

<span class="mw-page-title-main">Melevodopa/carbidopa</span> Combination dopaminergic medication

Melevodopa/carbidopa, sold under the brand name Sirio, is a combination of melevodopa, a prodrug of the dopamine precursor and hence non-selective dopamine receptor agonist levodopa (L-DOPA), and carbidopa, a peripherally selective aromatic L-amino acid decarboxylase (AAAD) inhibitor, which is used in the treatment of Parkinson's disease in Italy. It is taken orally in the form of tablets.

References

  1. 1 2 3 4 Hauser RA (2011). "Future treatments for Parkinson's disease: surfing the PD pipeline". The International Journal of Neuroscience. 121 Suppl 2: 53–62. doi:10.3109/00207454.2011.620195. PMID   22035030.
  2. 1 2 3 4 5 Ondo W (October 2014). "IPX066 , a mixed immediate/sustained-release levodopa preparation for Parkinson's disease". Expert Opinion on Pharmacotherapy. 15 (14): 2081–2085. doi:10.1517/14656566.2014.950224. PMID   25146967.
  3. 1 2 3 4 5 6 Freitas ME, Ruiz-Lopez M, Fox SH (November 2016). "Novel Levodopa Formulations for Parkinson's Disease". CNS Drugs. 30 (11): 1079–1095. doi:10.1007/s40263-016-0386-8. PMID   27743318.
  4. 1 2 3 "XP 21279". AdisInsight. Springer Nature Switzerland AG. 26 May 2022. Retrieved 27 September 2024.
  5. 1 2 3 Hengartner D, Fernandez HH (February 2019). "The next chapter in symptomatic Parkinson disease treatments". Parkinsonism & Related Disorders. 59. Elsevier BV: 39–48. doi:10.1016/j.parkreldis.2019.01.002. PMID   30661840.
  6. 1 2 Cacciatore I, Ciulla M, Marinelli L, Eusepi P, Di Stefano A (April 2018). "Advances in prodrug design for Parkinson's disease". Expert Opinion on Drug Discovery. 13 (4): 295–305. doi:10.1080/17460441.2018.1429400. PMID   29361853.
  7. ↑ "XP21279: Uses, Interactions, Mechanism of Action". DrugBank Online. 19 March 2008. Retrieved 27 September 2024.
  8. ↑ "Delving into the Latest Updates on XP-21279 with Synapse". Synapse. 20 September 2024. Retrieved 27 September 2024.
  9. ↑ "XP 21279". PubChem. Retrieved 27 September 2024.
  10. ↑ Markovic M, Deodhar S, Machhi J, Yeapuri P, Saleh M, J Edagwa B, et al. (February 2022). "Prodrug Therapies for Infectious and Neurodegenerative Diseases". Pharmaceutics. 14 (3): 518. doi: 10.3390/pharmaceutics14030518 . PMC   8953076 . PMID   35335894.
  11. ↑ Haddad F, Sawalha M, Khawaja Y, Najjar A, Karaman R (December 2017). "Dopamine and Levodopa Prodrugs for the Treatment of Parkinson's Disease". Molecules. 23 (1): 40. doi: 10.3390/molecules23010040 . PMC   5943940 . PMID   29295587.
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