Last update 01 Nov 2024

CACNA2D1

Last update 01 Nov 2024

Basic Info

Synonyms

CACNA2, CACNA2D1, CACNL2A

+ [11]

Introduction

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel (PubMed:35293990). Plays an important role in excitation-contraction coupling (By similarity).

Drugs associated with CACNA2D1

Crisugabalin

Target

CACNA2D1

Mechanism

CACNA2D1 blockers

Active Org.

Haisco Pharmaceutical Group Co., Ltd.

Originator Org.

Haisco Pharmaceutical Group Co., Ltd.

Active Indication

Neuralgia, Postherpetic [+6]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date15 May 2024

Mirogabalin Besilate

Target

CACNA2D1 x CACNA2D2

Mechanism

CACNA2D1 blockers [+1]

Active Org.

Daiichi Sankyo Co., Ltd. [+1]

Originator Org.

Daiichi Sankyo Co., Ltd.

Active Indication

Diabetic peripheral neuropathic pain [+1]

Inactive Indication

Chronic Kidney Diseases [+2]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date08 Jan 2019

Gabapentin Enacarbil

Target

CACNA2D1 x CACNA2D2

Mechanism

CACNA2D1 blockers [+1]

Active Org.

Azurity Pharmaceuticals, Inc. [+1]

Originator Org.

XenoPort, Inc.

Active Indication

Neuralgia, Postherpetic [+1]

Inactive Indication

Alcohol Use Disorder [+2]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date06 Apr 2011

1,763

Clinical Trials associated with CACNA2D1

NCT06614322 / Not yet recruitingPhase 2IIT

Sensory Phenotyping to Enhance Neuropathic Pain Drug Development (SPENDD): a Randomized, Double-blinded Cross-over Clinical Trial Aimed At Investigating Whether Bedside Quantitative Sensory Testing Can Predict Response to Analgesics.

The goal of this clinical trial is to determine whether quantitative sensory testing (QST) can be used to classify participants into pain sub-groups and predict who will respond best to certain pain treatments in participants with painful peripheral neuropathy.
The analgesic effect is evaluated by measuring pain intensity and Patient Global Impression of Change (PGIC).
This study is a 3-period cross-over trial. This means researchers will compare 3 different drugs (pregabalin, duloxetine, and placebo) over a period of 19 weeks.
Participants will:
* Undergo a quantitative sensory testing (QST) exam.
* Provide a blood sample.
* Complete questionnaires on the computer.
* Take the study drug as instructed.

Start Date01 Sep 2025

Sponsor / Collaborator

University of Rochester

[+1]

CTRI/2024/09/074067 / Not yet recruitingPhase 3IIT

Evaluation of efficacy and safety of add-on olanzapine plus pregabalin versus add-on aprepitant to ondansetron in preventing nausea and vomiting in patients undergoing highly emetogenic chemotherapy: A randomized, double-blind, add-on active-controlled, group-sequential and non-inferiority clinical trial - NIL

Start Date01 Nov 2024

Sponsor / Collaborator-

IRCT20190325043107N49 / SuspendedPhase 2/3IIT

Comparison of the effects of gabapentin plus different doses of dexamethasone in the management of acute pain after septoplasty

Start Date20 Oct 2024

Sponsor / Collaborator

Tabriz University of Medical Sciences

100 Clinical Results associated with CACNA2D1

100 Translational Medicine associated with CACNA2D1

0 Patents (Medical) associated with CACNA2D1

171

Literatures (Medical) associated with CACNA2D1

01 Nov 2024·Journal of Stroke and Cerebrovascular Diseases

Circulating circular RNAs as novel biomarkers and functional prediction for the early diagnosis in post-stroke cognitive impairment: A single-center prospective study in China

Article

Author: Liu, Qingxiang ; Chen, Qingmei ; Chen, Chen ; Zhang, Xianxian ; Fang, Qi ; Shen, Xiaozhu ; Chu, Zhaohu ; Yu, Liqiang ; Cao, Zhiyong ; Wang, Jianfei

BACKGROUNDEarly evaluation and intervention for post-stroke cognitive impairment are crucial for improving the prognosis of acute ischemic stroke. The search for specific diagnostic markers and feasible therapeutic targets is extremely urgent.The characteristics of circular RNAs make them promising candidates.AIMSTo screen circular RNAs as novel biomarkers and therapeutic targets for post-stroke cognitive impairment in large-artery atherosclerosis anterior circulation cerebral infarction patients.METHODSIn this prospective observational study, patients with first-ever large-artery atherosclerosis anterior circulation cerebral infarction were recruited. The Montreal Cognitive Assessment was used to assess the cognitive statuses of patients. Venous blood samples were collected on the seventh day after stroke onset. A circRNA microarray was used to identify differentially expressed circular RNAs in the discovery cohort (four patients with post-stroke cognitive impairment and four patients with post-stroke cognitive normal characteristics), and validation was performed in the validation cohorts (45 patients with post-stroke cognitive impairment and 30 patients with post-stroke cognitive normal characteristics) using quantitative real-time polymerase chain reaction. Receiver operating characteristic curves of the validated circular RNAs and the NIHSS score were constructed, and the area under the curve, sensitivity, and specificity were calculated. Correlation analysis was performed to explore the relationship between the copy number of circular RNAs and the cognitive status. The functions of the differentially expressed circular RNAs were predicted using bioinformatics analysis.RESULTSCircRNA microarray analysis revealed 189 human circular RNAs (152 upregulated and 37 downregulated) that were differentially expressed in the plasma samples of patients with post-stroke cognitive impairment and PSCN characteristics. The expression of hsa_circ_0089763, hsa_circ_0064644, and hsa_circ_0089762 was validated using quantitative real-time polymerase chain reaction. The area under the curve, sensitivity, and specificity of hsa_circ_0089762 in post-stroke cognitive impairment diagnosis were 0.993, 97.8%, and 96.7%, respectively, and the correlation coefficient between hsa_circ_0089762 expression and the Montreal Cognitive Assessment score was -0.693 (p < 0.001), which made it an ideal biomarker. Bioinformatic analysis revealed that the targeted mRNAs of the three circular RNAs were enriched in pathologically related signaling pathways of post-stroke cognitive impairment, such as the MAPK and PI3K-Akt signaling pathways. Based on the circRNA-miRNA-mRNA network, the three circular RNAs play a crucial role in numerous pathological processes of acute ischemic stroke and post-stroke cognitive impairment by sponging miRNAs such as MiR-335, MiR-424, and MiR-670. By building the protein-protein interaction network, we identified cluster 1 according to the MCODE score; cluster 1 was composed of ERBB4, FGFR1, CACNA2D1, NRG1, PPP2R5E, CACNB4, CACNB2, CCND1, NTRK2, and PTCH.CONCLUSIONHsa_circ_0089762, hsa_circ_0064644, and hsa_circ_0089763 are potential novel biomarkers and focal points for exploring intervention targets in post-stroke cognitive impairment of large-artery atherosclerosis anterior circulation cerebral infarction patients.REGISTRATION NUMBERChiCTR2000035074.

01 Sep 2024·Journal of Biological Chemistry

Nerve injury augments Cacna2d1 transcription via CK2-mediated phosphorylation of the histone deacetylase HDAC2 in dorsal root ganglia

Article

Author: Pan, Hui-Lin ; Chen, Shao-Rui ; Huang, Yuying ; Ghosh, Krishna

Development of chronic neuropathic pain involves complex synaptic and epigenetic mechanisms. Nerve injury causes sustained upregulation of α2δ-1 (encoded by the Cacna2d1 gene) in the dorsal root ganglion (DRG), contributing to pain hypersensitivity by directly interacting with and augmenting presynaptic NMDA receptor activity in the spinal dorsal horn. Under normal conditions, histone deacetylase 2 (HDAC2) is highly enriched at the Cacna2d1 gene promoter in the DRG, which constitutively suppresses Cacna2d1 transcription. However, nerve injury leads to HDAC2 dissociation from the Cacna2d1 promoter, promoting the enrichment of active histone marks and Cacna2d1 transcription in primary sensory neurons. In this study, we determined the mechanism by which nerve injury diminishes HDAC2 occupancy at the Cacna2d1 promoter in the DRG. Spinal nerve injury in rats increased serine-394 phosphorylation of HDAC2 in the DRG. Coimmunoprecipitation showed that nerve injury enhanced the physical interaction between HDAC2 and casein kinase II (CK2) in the DRG. Furthermore, repeated intrathecal treatment with CX-4945, a potent and specific CK2 inhibitor, markedly reversed nerve injury-induced pain hypersensitivity, HDAC2 phosphorylation, and α2δ-1 expression levels in the DRG. In addition, treatment with CX-4945 largely restored HDAC2 enrichment at the Cacna2d1 promoter and reduced the elevated levels of acetylated H3 and H4 histones, particularly H3K9ac and H4K5ac, at the Cacna2d1 promoter in the injured DRG. These findings suggest that nerve injury increases CK2 activity and CK2-HDAC2 interactions, which enhance HDAC2 phosphorylation in the DRG. This, in turn, diminishes HDAC2 enrichment at the Cacna2d1 promoter, thereby promoting Cacna2d1 transcription.

01 Sep 2024·Journal of Controlled Release

Evaluation of Pregabalin bioadhesive multilayered microemulsion IOP-lowering eye drops

Article

Author: Maria, Doaa N ; Jablonski, Monica M ; Ibrahim, Mohamed M ; Maria, Sara N ; White, William A ; Wang, XiangDi ; Kim, Minjae J ; Hollingsworth, T J

In spite of available treatment options, glaucoma continues to be a leading cause of irreversible blindness in the world. Current glaucoma medications have multiple limitations including: lack of sustained action; requirement for multiple dosing per day, ocular irritation and limited options for drugs with different mechanisms of action. Previously, we demonstrated that pregabalin, a drug with high affinity and selectivity for CACNA2D1, lowered IOP in a dose-dependent manner. The current study was designed to evaluate pregabalin microemulsion eye drops and to estimate its efficacy in humans using in silico methods. Molecular docking studies of pregabalin against CACNA2D1 of mouse, rabbit, and human were performed. Pregabalin microemulsion eye drops were characterized using multiple in vivo studies and its stability was evaluated over one year at different storage conditions. Molecular docking analyses and QSPR of pregabalin confirmed its suitability as a new IOP-lowering medication that functions using a new mechanism of action by binding to CACNA2D1 in all species evaluated. Because of its prolonged corneal residence time and corneal penetration enhancement, a single topical application of pregabalin ME can provide an extended IOP reduction of more than day in different animal models. Repeated daily dosing for 2 months confirms the lack of any tachyphylactic effect, which is a common drawback among marketed IOP-lowering medications. In addition, pregabalin microemulsion demonstrated good physical stability for one year, and chemical stability for 3-6 months if stored below 25 °C. Collectively, these outcomes greatly support the use of pregabalin eye drops as once daily IOP-lowering therapy for glaucoma management.

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CACNA2D1

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