Delving into the Latest Updates on API-001 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [3]

Target

σ1 receptor

Mechanism

σ1 receptor agonists(Sigma opioid receptor agonists)

Therapeutic Areas

Infectious DiseasesNervous System DiseasesEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

COVID-19Diabetic NeuropathiesNeuralgia, Postherpetic

Originator Organization

Esteve Pharmaceuticals S.A.

Active Organization-

Inactive Organization

Esteve Pharmaceuticals S.A.

Consorci Mar Parc de Salut de Barcelona

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC20H23N3O2

InChIKeyDGPGXHRHNRYVDH-UHFFFAOYSA-N

CAS Registry878141-96-9

View All Structures (2)

BACKGROUNDBinge drinking at adolescence is a risk factor for problematic alcohol (ethanol) consumption later in life, yet the murine studies that modelled this phenomenon via ethanol self-administration have provided mixed findings. Antagonism of the sigma-1 receptor (S1-R) system at adolescence modulates ethanol's motivational effects and intake. It is still unknown, however, whether this antagonism would protect against enhanced ethanol intake at adulthood after adolescent binge ethanol exposure.METHODSExp. 1 and 2 tested adults male or female Wistar rats -exposed or not to ethanol self-administration at adolescence (postnatal days 31-49; nine 2-hour sessions of access to 8-10% ethanol)- for ethanol intake using 24-h two-bottle choice test (Exp. 1) or time restricted, single-bottle, tests (Exp. 2). Experiments 2-5 evaluated, in adolescent or adult rats, the effects of the S1-R antagonist S1RA on ethanol intake and on ethanol-induced conditioned taste or place aversion. Ancillary tests (e.g., novel object recognition, ethanol-induced locomotor activity) were also conducted.RESULTSAdolescent ethanol exposure promoted ethanol consumption at both the restricted, single-bottle, and at the two-bottle choice tests conducted at adulthood. S1RA administration reduced ethanol intake at adulthood and facilitated the development of ethanol-induced taste (but not place) aversion.CONCLUSIONSS1RA holds promise for lessening ethanol intake after chronic and substantial ethanol exposure in adolescence that results in heightened ethanol exposure at adulthood. This putative protective effect of S1-R antagonism may relate to S1RA exacerbating the aversive effects of this drug.

12 Oct 2023·Biomedicines

Genetic and Pharmacological Blockade of Sigma-1 Receptors Attenuates Inflammation-Associated Hypersensitivity during Acute Colitis in CD1 Mice.

Article

Author: Carceller, Alicia ; López-Estévez, Sergio ; Aguilera, Mònica ; Gris, Georgia ; Martínez, Vicente ; de la Puente, Beatriz

Sigma-1 receptors (σ₁Rs) are implicated in nociception, including pain sensitization, and inflammation. We assessed the role of σ₁Rs on acute colitis-associated hypersensitivity using both genetic (constitutive knockout) and pharmacological blockade of the receptor. Colitis was induced in CD1 wild-type (WT) and σ₁R KO mice (exposure to dextran sodium sulfate, 3%). A von Frey test was used to assess referred mechanosensitivity (abdominal and plantar withdrawal responses). The effects of the selective σ₁R antagonists BD1063 and E-52862 were also assessed in WT animals. The expression of immune and sensory-related markers (RT-qPCR, Western blot) was assessed in the colon and lumbosacral spinal cord. The genetic ablation or pharmacological blockade of σ₁Rs attenuated acute colonic inflammation in a similar manner. Mechanosensitivity was similar in WT and σ₁R KO mice before colitis. In WT mice, but not in σ₁R KO, colitis was associated with the development of referred mechanical hypersensitivity, manifested as a reduction in the withdrawal thresholds to mechanical probing (paw and abdominal wall). In WT mice, BD1063 and E-52862 blocked colitis-associated hypersensitivity. A genotype- and treatment-related differential regulation of sensory-related markers was detected locally (colon) and within the spinal cord. σ₁Rs are involved in the development of acute intestinal inflammation and its associated referred mechanical hypersensitivity. The selective modulation of sensory-related pathways within the colon and spinal cord might be part of the underlying mechanisms. These observations support the pharmacological use of σ₁R antagonists for the treatment of intestinal inflammation-induced hypersensitivity.

01 Oct 2023·Pharmacological reports : PR

Novel object recognition test as an alternative approach to assessing the pharmacological profile of sigma-1 receptor ligands.

Article

Author: Bojarski, Andrzej J ; Szczepańska, Katarzyna ; Malikowska-Racia, Natalia ; Popik, Piotr

BACKGROUNDAlthough the terms "agonist" and "antagonist" have been used to classify sigma-1 receptor (σ₁R) ligands, an unambiguous definition of the functional activity is often hard. In order to determine the pharmacological profile of σ₁R ligands, the most common method is to assess their potency to alleviate opioid analgesia. It has been well established that σ₁R agonists reduce opioid analgesic activity, while σ₁R antagonists have been demonstrated to enhance opioid analgesia in different pain models.METHODSIn the present study, we evaluated the pharmacological profile of selected σ₁R ligands using a novel object recognition (NOR) test, to see if any differences in cognitive functions between σ₁R agonists and antagonists could be observed. We used the highly selective PRE-084 and S1RA as reference σ₁R agonist and antagonist, respectively. Furthermore, compound KSK100 selected from our ligand library was also included in this study. KSK100 was previously characterized as a dual-targeting histamine H₃/σ₁R antagonist with antinociceptive and antiallodynic activity in vivo. Donepezil (acetylcholinesterase inhibitor and σ₁R agonist) was used as a positive control drug.RESULTSBoth tested σ₁R agonists (donepezil and PRE-084) improved learning in the NOR test, which was not observed with the σ₁R antagonists S1RA and KSK100.CONCLUSIONSThe nonlinear dose-response effect of PRE-084 in this assay does not justify its use for routine assessment of the functional activity of σ₁R ligands.

100 Deals associated with API-001

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 2	ES	Consorci Mar Parc de Salut de Barcelona	16 Oct 2020
Neuralgia, Postherpetic	Phase 2	ES	Esteve Pharmaceuticals S.A.	17 Jul 2012
Diabetic Neuropathies	Phase 2	ES	Esteve Pharmaceuticals S.A.	13 Jun 2012