Devapamil

Last updated
Devapamil
Devapamil.svg
Names
IUPAC name
(RS)-2-(3,4-dimethoxyphenyl)-2-isopropyl-5-[2-(3-methoxyphenyl)ethyl-methylamino]pentanenitrile
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
PubChem CID
UNII
  • InChI=1/C26H36N2O3/c1-20(2)26(19-27,22-11-12-24(30-5)25(18-22)31-6)14-8-15-28(3)16-13-21-9-7-10-23(17-21)29-4/h7,9-12,17-18,20H,8,13-16H2,1-6H3
    Key: VMVKIDPOEOLUFS-UHFFFAOYAV
  • N#CC(c1cc(OC)c(OC)cc1)(CCCN(CCc2cccc(OC)c2)C)C(C)C
Properties
C26H36N2O3
Molar mass 424.585 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Devapamil is a calcium channel blocker. It is also known as desmethoxyverapamil, which is a phenylalkylamine (PAA) derivative. [1] Devapamil not only inhibits by blocking the calcium gated channels, but also by depolarizing the membrane during the sodium-potassium exchanges. [2]

Contents

Structure

Devapamil consists of two aromatic rings with methoxy substituents connected by an alkylamine chain increasing flexibility and overall potency. [3]

Animal studies

Devapamil in rats can be used to decrease glutathione levels and increase oxidation of lipids, which makes it effective in preclusion of ulcers caused by stress. [4] [5] The medical characteristics of this drug, and other phenylalkylamines, depends greatly on the state of the calcium channels being targeted which results in a greater affinity and drug efficiency. [6]

Related Research Articles

Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate, to prevent peripheral and cerebral vasospasm, and to reduce chest pain caused by angina pectoris.

Ryanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in different signaling pathways involving calcium release from intracellular organelles. The RYR2 ryanodine receptor isoform is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells.

<span class="mw-page-title-main">Oxidative stress</span> Free radical toxicity

Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O
2
, OH and H2O2. Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling.

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Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.

<span class="mw-page-title-main">SYT1</span> Protein-coding gene in the species Homo sapiens

Synaptotagmin-1 is a protein that in humans is encoded by the SYT1 gene.

<span class="mw-page-title-main">Trypanothione synthase</span> Class of enzymes

In enzymology, a trypanothione synthase (EC 6.3.1.9) is an enzyme that catalyzes the chemical reaction

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Alpha-actinin-1 is a protein that in humans is encoded by the ACTN1 gene.

<span class="mw-page-title-main">Calsenilin</span> Protein found in humans

Calsenilin is a protein that in humans is encoded by the KCNIP3 gene.

<span class="mw-page-title-main">CAMK1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">KCNIP2</span> Protein-coding gene in the species Homo sapiens

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Peroxiredoxin-6 is a protein that in humans is encoded by the PRDX6 gene. It is a member of the peroxiredoxin family of antioxidant enzymes.

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<span class="mw-page-title-main">ATP2A3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CACNB4</span> Protein-coding gene in humans

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<span class="mw-page-title-main">ITPR3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">ML-SI3</span> Chemical compound

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References

  1. Erdmann R, Lüttgau HC (June 1989). "The effect of the phenylalkylamine D888 (devapamil) on force and Ca2+ current in isolated frog skeletal muscle fibres". The Journal of Physiology. 413 (1): 521–41. doi:10.1113/jphysiol.1989.sp017667. PMC   1189114 . PMID   2557440.
  2. Dierkes PW, Wende V, Hochstrate P, Schlue WR (July 2004). "L-type Ca2+ channel antagonists block voltage-dependent Ca2+ channels in identified leech neurons". Brain Research. 1013 (2): 159–67. doi:10.1016/j.brainres.2004.03.038. PMID   15193524. S2CID   22004238.
  3. Cheng RC, Tikhonov DB, Zhorov BS (October 2009). "Structural model for phenylalkylamine binding to L-type calcium channels". The Journal of Biological Chemistry. 284 (41): 28332–42. doi: 10.1074/jbc.M109.027326 . PMC   2788883 . PMID   19700404.
  4. Alican I, Toker F, Arbak S, Yegen BC, Yalçin AS, Oktay S (August 1994). "Gastric lipid peroxidation, glutathione and calcium channel blockers in the stress-induced ulcer model in rats". Pharmacological Research. 30 (2): 123–35. doi:10.1016/1043-6618(94)80004-9. PMID   7816741.
  5. Hung CR (May 2004). "Protective effects of lysozyme chloride and reduced glutathione on betel quid chewing-produced gastric oxidative stress and haemorrhagic ulcer in rats". Inflammopharmacology. 12 (2): 115–29. doi:10.1163/1568560041352284. PMID   15265315. S2CID   860321.
  6. Cheng RC, Tikhonov DB, Zhorov BS (October 2009). "Structural model for phenylalkylamine binding to L-type calcium channels". The Journal of Biological Chemistry. 284 (41): 28332–42. doi: 10.1074/jbc.M109.027326 . PMC   2788883 . PMID   19700404.