Last update 01 Nov 2024

CACNA1H

Last update 01 Nov 2024

Basic Info

Synonyms

CACNA1H, calcium channel, voltage-dependent, T type, alpha 1H subunit, calcium voltage-gated channel subunit alpha1 H

+ [4]

Introduction

Voltage-sensitive calcium channel that gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group. A particularity of this type of channel is an opening at quite negative potentials, and a voltage-dependent inactivation (PubMed:9670923, PubMed:9930755, PubMed:27149520). T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle (Probable). They may also be involved in the modulation of firing patterns of neurons (PubMed:15048902). In the adrenal zona glomerulosa, participates in the signaling pathway leading to aldosterone production in response to either AGT/angiotensin II, or hyperkalemia (PubMed:25907736, PubMed:27729216).

Drugs associated with CACNA1H

Flunarizine

Target

CACNA1G x CACNA1H x CACNA1I

Mechanism

CACNA1G blockers [+2]

Active Org.

The Chinese University of Hong Kong [+1]

Originator Org.

Janssen Pharmaceuticals, Inc.

Active Indication

Migraine Disorders [+2]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Icariside II

Target

CACNA1H

Mechanism

CACNA1H blockers

Active Org.

Zymedyne Therapeutics, Inc.Startup [+1]

Originator Org.

University of Calgary [+1]

Active Indication

Inflammation [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CU-00213

Target

CACNA1H

Mechanism

CACNA1H blockers

Active Org.

Acurex Biosciences Corp.

Originator Org.

Acurex Biosciences Corp.

Active Indication

Parkinson Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with CACNA1H

NCT06499116 / Not yet recruitingPhase 4IIT

Comparison of the Effectiveness of First-line Preventive Treatment of Migraine in Primary Care: a Pragmatic Clinical Trial [PREMI Study]

This study, which is aimed at comparing the effectiveness of the most frequently used drugs in the first line in primary care for the preventive treatment of migraine (amitriptyline, flunarizine, topiramate and propranolol), is a multicentre, pragmatic, parallel group, open randomised trial. Adults (≥18) candidates for preventive treatment for migraine; those with a frequency of ≥4 monthly migraine days, and who agree to participate in the clinical trial, will be randomised to one of the 4 groups. Sample: 460 patients. The primary outcome will be the reduction in monthly migraine days, comparing amitriptyline, flunarizine and topiramate with propranolol.

Start Date01 Oct 2024

Sponsor / Collaborator

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

[+1]

NCT06162819 / Not yet recruitingNot ApplicableIIT

Efficacy of Flunarizine Vs Amitriptyline in Prophylaxis of Migraine Prophylaxis

To compare the frequency of acute attack and mean pain score ( assessed by visual analog scale) among subjects using either flunarizine or amitriptyline among patients with migraine coming to tertiary care Hospital in Lahore, Pakistan.
In this study 84 patients with migraine Age ranged between 18- 60 years, Both genders having 3 or more migraine attacks per month, normal systemic and neurological examination and not having taken any prophylactic medication for the last 4 months will randomly divided into two equal group of 42 subjects each.

Start Date01 Jan 2024

Sponsor / Collaborator-

CTR20233648 / CompletedNot Applicable

盐酸氟桂利嗪胶囊在中国健康受试者中进行的单中心、随机、开放、单次（餐后）口服给药、两制剂、两序列、两周期、交叉的人体生物等效性试验

[Translation] A single-center, randomized, open-label, single (postprandial) oral bioequivalence study of flunarizine hydrochloride capsules in healthy Chinese subjects: two-formulation, two-sequence, two-period, crossover

主要目的：观察中国健康受试者在餐后状态下单次口服受试制剂盐酸氟桂利嗪胶囊（规格：5mg（以氟桂利嗪计）；生产企业：郑州瑞康制药有限公司）和参比制剂盐酸氟桂利嗪胶囊（商品名：西比灵®；规格：5mg（以氟桂利嗪计）；生产企业：西安杨森制药有限公司；持证商：西安杨森制药有限公司）后的药代动力学特征，评价餐后状态下两种制剂的生物等效性。次要目的：观察受试制剂盐酸氟桂利嗪胶囊和参比制剂盐酸氟桂利嗪胶囊（西比灵®）在中国健康受试者中的安全性。

[Translation]

Primary objective: To observe the pharmacokinetic characteristics of the test preparation Flunarizine Hydrochloride Capsules (Specification: 5 mg (calculated as flunarizine); Manufacturer: Zhengzhou Ruikang Pharmaceutical Co., Ltd.) and the reference preparation Flunarizine Hydrochloride Capsules (Trade name: Sibelion®; Specification: 5 mg (calculated as flunarizine); Manufacturer: Xi'an Janssen Pharmaceutical Co., Ltd.; Licensee: Xi'an Janssen Pharmaceutical Co., Ltd.) after a single oral administration in the fed state in healthy Chinese subjects, and to evaluate the bioequivalence of the two preparations in the fed state. Secondary objective: To observe the safety of the test preparation Flunarizine Hydrochloride Capsules and the reference preparation Flunarizine Hydrochloride Capsules (Sibelion®) in healthy Chinese subjects.

Start Date16 Dec 2023

Sponsor / Collaborator

Zhengzhou Ruikang Pharmaceutical Co., Ltd

100 Clinical Results associated with CACNA1H

100 Translational Medicine associated with CACNA1H

0 Patents (Medical) associated with CACNA1H

599

Literatures (Medical) associated with CACNA1H

01 Dec 2024·Molecular Genetics and Genomics

CACNA1H restrains chemotherapy resistance in ovarian clear cell carcinoma cells by repressing autophagy

Article

Author: Jiang, Xinyan ; Zheng, Liang ; Chen, Hongju ; Shi, Huaijing

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer and is highly malignant with high chemoresistance. CACNA1H is pivotal in tumor development. However, the role of CACNA1H in the acquisition process of chemotherapeutic resistance in OCCC cells is rarely reported. Therefore, this study aimed to explore the role of CACNA1H in chemotherapy resistance of OCCC cells and its related mechanism. Based on bioinformatics analysis, we found that CACNA1H was downregulated in chemoresistant OCCC patients compared to chemosensitive OCCC patients. Comparing DDP-resistant and sensitive OCCC cell lines, the resistant strain showed lower CACNA1H mRNA expression. CACNA1H expression was associated with calcium signaling pathways in chemoresistant OCCC patients. CACNA1H mRNA expression was significantly downregulated in OCCC cells compared to normal ovarian epithelial cells. When CACNA1H was overexpressed, intracellular Ca²⁺ concentration and protein levels of p-CaMKII and p-Akt were significantly upregulated, while protein levels of LC3-II/LC3-I and Beclin1 were downregulated, indicating a repression of autophagy. The rescue experiment revealed that CACNA1H overexpression in drug-resistant OCCC cells reduced autophagy-induced DDP resistance via CaMKII/Akt signaling. Overall, CACNA1H increased intracellular Ca²⁺ concentration and activated CaMKII/Akt signaling pathway in OCCC, thereby repressing autophagy to maintain the sensitivity of OCCC cells to DDP.

01 Dec 2024·Pediatric Neurology

Comparative Analysis of Lennox-Gastaut Syndrome With Different Subtypes of Tonic Seizures: A Single-Center Retrospective Cohort Study

Article

Author: Lin, Yicong ; Wang, Yuping ; Zhao, Xuan ; Zhang, Liping ; Qi, Xiaohong ; Wang, Shiyu ; Jia, Yu ; Li, Ting

BACKGROUNDLennox-Gastaut syndrome (LGS) is one of the most severe childhood-onset epileptic encephalopathies, primarily characterized by tonic seizures. In clinical practice, we have identified various subtypes of tonic seizures in LGS. This study aimed to analyze the clinical characteristics, electrographic features, treatment responses, and prognosis across different subtypes of LGS.METHODSThis retrospective cohort study included 46 patients diagnosed with LGS at our center between January 2017 and January 2020. Patients were classified into four groups based on tonic seizure subtypes: Group A (tonic), Group B (spasm-tonic), Group C (myoclonic-tonic), and Group D (combination of spasm-tonic and myoclonic-tonic). Comprehensive clinical data were collected and analyzed.RESULTSOf the 46 patients, 33 were male. The mean age of onset for Group B (12.38 ± 7.85 months) was significantly less than those of the other three groups (P = 0.02). No significant differences in etiology were found among the groups. Genetic analysis identified mutations in SCN8A, MCCC2, STXBP1, GABRB3, and CACNA1H. After a minimum follow-up of 24 months, the treatment outcomes were more favorable in Groups A and C, whereas psychomotor development was notably poorer in Groups B and D.CONCLUSIONSThe findings of this study suggest that LGS may present with distinct subtypes of tonic seizures, with spasm-tonic seizures presenting at an earlier age. Patients with LGS experiencing spasm-tonic seizures, with or without myoclonic-tonic seizures, exhibited poorer treatment responses and psychomotor development than those with other subtypes.

01 Dec 2024·Gene

Cav3.2 deletion attenuates nonalcoholic fatty liver disease in mice

Article

Author: Hu, Chengyun ; Zhou, Wanjun ; Jiang, Lai ; Dai, Feibiao ; Li, Chuanyao ; Li, Xue ; Tang, Chaoliang ; Wang, Zhen ; Wang, Jiawu ; Luo, Shanshan ; Long, Tengfei ; Chen, Hao

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and represents the main cause of liver cirrhosis and hepatocellular carcinoma. Cav3.2 is a T-type calcium channel that is widely present in tissues throughout the body and plays a vital role in energy and metabolic balance. However, the effects of Cav3.2 on the NFALD remain unclear. Here, we investigated the role of Cav3.2 channel in the development and progression of NAFLD. After 16 weeks on a high-fat diets (HFD), Cav3.2 knockout (Cav3.2 KO) improved hepatic steatosis, liver injury and metabolic syndrome in an NAFLD mouse model. We provided evidence that Cav3.2 KO inhibited HFD-induced hepatic oxidative stress, inflammation and hepatocyte apoptosis. In addition, Cav3.2 KO also attenuated hepatic lipid accumulation, oxidative stress, inflammation and hepatocyte apoptosis in palmitic acid/oleic acid (PAOA)-treated primary hepatocytes. These results suggest that therapeutic approaches targeting Cav3.2 provide effective approaches for treating NAFLD.

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CACNA1H

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