Preliminary <i>in vitro</i> approach to evaluate the drug-drug interaction potential of EST73502, a dual µ-opioid receptor partial agonist and σ1 receptor antagonist

Ayet, Eva; Yeste, Sandra; Reinoso, Raquel F.; Pretel, María José; Balada, Ariadna; Serafini, Maria Teresa

doi:10.1080/00498254.2021.1877850

Cited by 2 publications

(3 citation statements)

References 37 publications

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“…administration of WLB-73502 at 3 mg/kg (PK parameters summarized in Table 2 ) were 127.6–236.5 ng/g, that correspond to a brain concentration of 362.0–671.1 nmol/kg. Considering the brain tissue binding of WLB-73502 in the rat (49.9%) 41 , the free, unbound fraction corresponds to 181.4–336.2 nmol/kg. As a reference, the binding to human MOR and S1R is 64 and 118 nmol/L, respectively 28 .…”

Section: Resultsmentioning

confidence: 99%

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Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids

Vidal-Torres¹,

Fernández‐Pastor²,

Garcia³

et al. 2023

Acta Pharmaceutica Sinica B

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Section: Resultsmentioning

confidence: 99%

“…Brain concentrations obtained from experimental quantifications at 15 and 30 min after compound administration. Unbound, free fraction was calculated subtracting the bound fraction (rat brain tissue binding: 49.9%) 41 . Binding affinities ( K i ) in vitro correspond to human MOR and S1R 28 .…”

Section: Resultsmentioning

confidence: 99%

Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids

Vidal-Torres¹,

Fernández‐Pastor²,

Garcia³

et al. 2023

Acta Pharmaceutica Sinica B

Self Cite

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“…A candidate drug (EST73502, Esteve Pharmaceuticals, Barcelona, Spain) was selected and evaluated in preclinical studies. It has entered clinical trials for the treatment of pain associated with osteoarthritis as the first dual µ-opioid receptor agonist/σ1 receptor antagonist [ 12 , 13 ]. This drug might be considered the first-in-class bifunctional compound [ 10 ].…”

Section: Reviewmentioning

confidence: 99%

The Emerging Role of Sigma Receptors in Pain Medicine

Pergolizzi¹,

Varrassi²

2023

Cureus

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Sigma receptors are protein chaperones with the unexpected characteristic of being activated by ligand binding. As such, they represent intriguing new targets for potential drug development. As a protein chaperone, these "receptors" escort proteins from the endoplasmic reticulum to their destinations and act to correct misfolded proteins. The two subtypes of sigma receptors, named σ1 and σ2, are markedly distinct from each other. Agonists and antagonists at these receptors show promise as new drug targets, addressing a range of diseases including neurodegenerative disorders, cancer, and cardiac disorders, and may also be analgesic agents and rehabilitation drugs for opioid use disorder. As an analgesic, sigma receptors seem to be more effective in treating neuropathic than nociceptive pain. New bifunctional compounds are being developed with opioids, because agents targeting sigma receptors may have an opioidsparing effect. The pipeline of agents based on the sigma receptors is long and may treat things from Fragile X syndrome to Parkinson's disease to Huntington's disease to cancer. A novel agent ADV502 acts as a highaffinity σ1 antagonist and partial agonist at the µ-opioid receptor and may be an important agent both for the treatment of neuropathic cancer pain and for rehabilitation of opioid use disorder. Since there has been little recent innovation in pain medicine regarding new compounds and drug targets, drugs that affect the sigma receptor system seem promising and encouraging.

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Preliminary in vitro approach to evaluate the drug-drug interaction potential of EST73502, a dual µ-opioid receptor partial agonist and σ1 receptor antagonist

Cited by 2 publications

References 37 publications

Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids

Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids

The Emerging Role of Sigma Receptors in Pain Medicine

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