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]

100 Clinical Results associated with CACNA1G x CACNA1I x CACNA1H

100 Translational Medicine associated with CACNA1G x CACNA1I x CACNA1H

0 Patents (Medical) associated with CACNA1G x CACNA1I x CACNA1H

Literatures (Medical) associated with CACNA1G x CACNA1I x CACNA1H

01 Oct 2023·Molecular pharmacology

Englerin A Inhibits T-Type Voltage-Gated Calcium Channels at Low Micromolar Concentrations.

Article

Author: Schneider, Jochen G ; Klugbauer, Norbert ; Wardas, Barbara ; Beck, Andreas ; Flockerzi, Veit

Englerin A (EA) is a potent agonist of tetrameric transient receptor potential canonical (TRPC) ion channels containing TRPC4 and TRPC5 subunits. TRPC proteins form cation channels that are activated by plasma membrane receptors. They convert extracellular signals such as angiotensin II into cellular responses, whereupon Na⁺ and Ca²⁺ influx and depolarization of the plasma membrane occur. Via depolarization, voltage-gated Ca²⁺ (CaV) channels can be activated, further increasing Ca²⁺ influx. We investigated the extent to which EA also affects the functions of CaV channels using the high-voltage-activated L-type Ca²⁺ channel CaV1.2 and the low-voltage-activated T-type Ca²⁺ channels CaV3.1, CaV3.2, and CaV3.3. After expression of cDNAs in human embryonic kidney (HEK293) cells, EA inhibited currents through all T-type channels at half-maximal inhibitory concentrations (IC₅₀) of 7.5 to 10.3 μM. In zona glomerulosa cells of the adrenal gland, angiotensin II-induced elevation of cytoplasmic Ca²⁺ concentration leads to aldosterone release. We identified transcripts of low- and high-voltage-activated CaV channels and of TRPC1 and TRPC5 in the human adrenocortical (HAC15) zona glomerulosa cell line. Although no EA-induced TRPC activity was measurable, Ca²⁺ channel blockers distinguished T- and L-type Ca²⁺ currents. EA blocked 60% of the CaV current in HAC15 cells and T- and L-type channels analyzed at -30 mV and 10 mV were inhibited with IC₅₀ values of 2.3 and 2.6 μM, respectively. Although the T-type blocker Z944 reduced basal and angiotensin II-induced 24-hour aldosterone release, EA was not effective. In summary, we show here that EA blocks CaV1.2 and T-type CaV channels at low-micromolar concentrations. SIGNIFICANCE STATEMENT: In this study we showed that englerin A (EA), a potent agonist of tetrameric transient receptor potential canonical (TRPC)4- or TRPC5-containing channels and currently under investigation to treat certain types of cancer, also inhibits the L-type voltage-gated Ca²⁺ (CaV) channel CaV1.2 and the T-type CaV channels CaV3.1, CaV3.2, and CaV3.3 channels at low micromolar concentrations.

01 Aug 2022·Heliyon

Insights on possible interplay between epithelial-mesenchymal transition and T-type voltage gated calcium channels genes in metastatic breast carcinoma

Article

Author: Ragab Ibrahim, Fawziya A E ; Yousef, Amany I ; Ahmed, Ayman Farouk Mohammad ; Naser Hussein, Zain Ulabdeen ; Abd El Moneim, Nadia Ahmed ; Hussein, Amr Mahmoud ; Al-Masry, O ; Ragab, Noha Mohamed

Breast cancer (BC) is the most common life-threatening malignancy amongst women with high incidence worldwide. In Egypt, it is the most known malignancy amongst females. Epithelial-mesenchymal transition (EMT) participates in breast tumors' invasiveness, and metastasis, but the process is poorly understood. The involvement of voltage-gated calcium channels signaling in EMT has not yet been fully explored. Therefore, the aim of this study was to investigate the possible role of T-type calcium channels in metastasis and EMT among breast cancer patients. The study was carried out on 48 female breast cancer patients who were divided into two groups; metastatic and non-metastatic. qRT-PCR was employed to measure the expression of EMT marker genes (N- cadherin, E-cadherin, Snail, Vimentin and T-type VGCCs genes (CACNA1G, CACNA1H, and CACNA1I). The results of the present study revealed differential expression of the EMT marker genes in blood and tissue of non-metastatic and metastatic breast cancer patients, with a clear tendency for the mesenchymal markers to be significantly elevated in metastatic patients as well as malignant tissues taken from non-metastatic patients as compared to their paired tumor adjacent normal (TAN) tissue. Both CACNA1H and CACNA1I (T-type VGCCs oncogenes) were significantly elevated in blood of metastatic patients when compared to non-metastatic ones. In contrast, CACNA1G (tumor suppressor) exhibited a significant decrease in metastatic patients. The strong correlation between the expression of T-type VGCCs and mesenchymal marker genes in metastatic breast cancer patients casts light on the role of T-type VGCCs in metastasis and their involved in tumor invasiveness.

01 Dec 2021·Molecular BrainQ3 · MEDICINE

Modeling temperature- and Cav3 subtype-dependent alterations in T-type calcium channel mediated burst firing

Q3 · MEDICINE

ArticleOA

Author: Turner, Ray W ; Fernandez, Fernando R ; Zamponi, Gerald W ; Iftinca, Mircea C

AbstractT-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.

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