Pridopidine

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Chemical compound

title: "Pridopidine" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["benzosulfones", "d2-antagonists", "huntington's-disease", "4-phenylpiperidines", "sigma-agonists", "propyl-compounds", "mesyl-compounds"] description: "Chemical compound" topic_path: "general/benzosulfones" source: "https://en.wikipedia.org/wiki/Pridopidine" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

::data[format=table title="Infobox drug"]

FieldValue
imagePridopidine.svg
image_classskin-invert-image
ATC_prefixN07
ATC_suffixXX26
CAS_number346688-38-8
PubChem9795739
DrugBankDB05371
ChemSpiderID7971505
UNIIHD4TW8S2VK
KEGGD09953
ChEMBL596802
IUPAC_name4-(3-methylsulfonylphenyl)-1-propylpiperidine
C15
SMILESCCCN1CCC(CC1)C2=CC(=CC=C2)S(=O)(=O)C
StdInChI1S/C15H23NO2S/c1-3-9-16-10-7-13(8-11-16)14-5-4-6-15(12-14)19(2,17)18/h4-6,12-13H,3,7-11H2,1-2H3
StdInChIKeyYGKUEOZJFIXDGI-UHFFFAOYSA-N
::

| image = Pridopidine.svg | image_class = skin-invert-image | width = | alt = | caption =

| pronounce = | tradename = | Drugs.com = | MedlinePlus = | DailyMedID = | pregnancy_AU = | pregnancy_category = | routes_of_administration = | class = | ATC_prefix = N07 | ATC_suffix = XX26

| legal_status =

| bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =

| CAS_number = 346688-38-8 | CAS_supplemental = | PubChem = 9795739 | IUPHAR_ligand = | DrugBank = DB05371 | ChemSpiderID = 7971505 | UNII = HD4TW8S2VK | KEGG = D09953 | ChEBI = | ChEMBL = 596802 | NIAID_ChemDB = | PDB_ligand = | synonyms =

| IUPAC_name = 4-(3-methylsulfonylphenyl)-1-propylpiperidine | C=15 | H=23 | N=1 | O=2 | S=1 | SMILES = CCCN1CCC(CC1)C2=CC(=CC=C2)S(=O)(=O)C | StdInChI = 1S/C15H23NO2S/c1-3-9-16-10-7-13(8-11-16)14-5-4-6-15(12-14)19(2,17)18/h4-6,12-13H,3,7-11H2,1-2H3 | StdInChIKey = YGKUEOZJFIXDGI-UHFFFAOYSA-N

Pridopidine (developmental code name PL-101) is an orally administrated small molecule investigational drug. Pridopidine is a selective and potent sigma-1 receptor agonist. It is being developed by Prilenia Therapeutics and is currently in late-stage clinical development for Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS).

Mechanism of action

Pridopidine works by binding and activating an intracellular protein called the sigma-1 receptor (S1R) located at the mitochondria-associated membrane (MAM) of the endoplasmic reticulum. The S1R regulates key cellular processes crucial to neuronal health and survival. Selective activation of the S1R is a promising therapeutic target for treating neurodegenerative and neurodevelopmental disorders.

Pridopidine activation of the S1R demonstrates neuroprotective effects in numerous models of neurodegenerative diseases including HD, ALS, Glaucoma, Parkinson's disease (PD) and Alzheimer's disease (AD).

Pridopidine exhibits a neuroprotective effect against mutant Huntingtin (mHTT)-induced cell death in mouse primary HD neurons and human HD-induced pluripotent stem cells. It restores the impaired synaptic plasticity in HD neurons, enhances mitochondrial function, upregulates BDNF transport and secretion, reduces endoplasmic reticulum stress and restores dendritic spine abnormalities in HD and AD models. In models of ALS, pridopidine protects neuron-muscle connectivity and restores muscle integrity and contractility. These beneficial effects are exclusively mediated by the S1R as either deletion of this gene, or selective inhibition of its function, completely abolish pridopidine's beneficial effects.

Initially, the primary target of pridopidine was postulated to be the dopamine D2/D3 receptors. However, in vitro binding assays show that pridopidine has high affinity for the S1R and low affinity for other targets including the dopamine D2/D3 receptors, adrenergic a2c receptor and the Sigma-2 receptor. Furthermore, selective and robust occupancy of the S1R, with no or negligible occupancy of the D2/D3 receptors was demonstrated by in vivo positron emission tomography (PET) imaging studies in rats and human.

Potential indications

Huntington's disease

Huntington's disease (HD) is a progressive fatal neurodegenerative disease caused by a mutation in the Huntingtin gene (expanded CAG repeat * *35). The disease is characterized by progressive motor abnormalities, cognitive decline, and psychiatric and behavioral symptoms. Adult-onset HD usually begins between 35 and 45 years of age. Following onset, motor, cognitive and functional outcomes steadily decline over 15 to 20 years, ultimately leading to a state of profound incapacity and death. The disease is inherited in an autosomal dominant manner, and thus each child of a parent with HD has a 50% chance of inheriting the mutated HD gene. For patients and their families, maintaining functional capacity is vital as it translates to a patient's ability to maintain their occupation, continue to manage their daily lives, and live independently.

A meta-analysis of four randomized controlled trials (RCTs) involving 1,130 patients (816 in the pridopidine group and 314 in the placebo group) found that pridopidine led to a slight, though not statistically significant, improvement in overall motor symptoms, as measured by the Unified Huntington's Disease Rating Scale Total Motor Score, compared to placebo. However, the drug significantly improved voluntary movements, as indicated by the Modified Motor Score. Pridopidine was generally well tolerated, with no significant differences in adverse events or serious adverse events compared to placebo. The findings suggest that pridopidine has potential for treating motor symptoms in HD, with a favorable safety profile, warranting further clinical trials to confirm its benefits.

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating progressive fatal neurodegenerative disease characterized by upper and lower motor neuron degeneration. Over time this progressive loss of motor function leads to losing the ability to speak, eat, move and eventually breathe.

Society and culture

Legal status

In July 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) recommended the refusal of a marketing authorization for Nurzigma, a medicine intended for the treatment of adults with Huntington's disease.

References

References

  1. (March 2019). "Targeting the Sigma-1 Receptor via Pridopidine Ameliorates Central Features of ALS Pathology in a SOD1G93A Model". Cell Death & Disease.
  2. (November 2021). "Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma". Scientific Reports.
  3. (April 2019). "Pridopidine Induces Functional Neurorestoration Via the Sigma-1 Receptor in a Mouse Model of Parkinson's Disease". Neurotherapeutics.
  4. (September 2019). "Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor". Neurobiology of Disease.
  5. (2019). "Impairment and Restoration of Homeostatic Plasticity in Cultured Cortical Neurons From a Mouse Model of Huntington Disease". Frontiers in Cellular Neuroscience.
  6. (April 2021). "The Sigma-1 Receptor Mediates Pridopidine Rescue of Mitochondrial Function in Huntington Disease Models". Neurotherapeutics.
  7. (January 2017). "The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease". Neurobiology of Disease.
  8. (April 2019). "Pridopidine stabilizes mushroom spines in mouse models of Alzheimer's disease by acting on the sigma-1 receptor". Neurobiology of Disease.
  9. (July 2021). "Pridopidine reduces mutant huntingtin-induced endoplasmic reticulum stress by modulation of the Sigma-1 receptor". Journal of Neurochemistry.
  10. (September 2016). "Pridopidine activates neuroprotective pathways impaired in Huntington Disease". Human Molecular Genetics.
  11. (May 2019). "Pridopidine, a clinic-ready compound, reduces 3,4-dihydroxyphenylalanine-induced dyskinesia in Parkinsonian macaques". Movement Disorders.
  12. (April 2021). "Sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine in healthy volunteers and patients with Huntington disease: a [18F] fluspidine and [18F] fallypride PET study". European Journal of Nuclear Medicine and Molecular Imaging.
  13. (September 2015). "Pridopidine selectively occupies sigma-1 rather than dopamine D2 receptors at behaviorally active doses". Psychopharmacology.
  14. (January 2018). "Huntington's disease: a clinical review". European Journal of Neurology.
  15. (March 1993). "A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group". Cell.
  16. (March 1996). "Unified Huntington's Disease Rating Scale: reliability and consistency. Huntington Study Group". Movement Disorders.
  17. (March 2016). "Huntington's Disease". U.S. Food and Drug Administration (FDA).
  18. (January 2022). "The Efficacy and Safety of Pridopidine on Treatment of Patients with Huntington's Disease: A Systematic Review and Meta-Analysis". Movement Disorders Clinical Practice.
  19. (2021-07-25). "Amyotrophic Lateral Sclerosis". Exon Publications.
  20. (25 July 2025). "Nurzigma EPAR".

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benzosulfonesd2-antagonistshuntington's-disease4-phenylpiperidinessigma-agonistspropyl-compoundsmesyl-compounds