Budiodarone

Source: Wikipedia, the free encyclopedia.
Budiodarone
Clinical data
ATC code
  • None
Legal status
Legal status
Identifiers
  • [(2S)-butan-2-yl] 2-[3-[4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl]-1-benzofuran-2-yl]acetate
JSmol)
  • Ic1cc(cc(I)c1OCCN(CC)CC)C(=O)c2c3ccccc3oc2CC(=O)O[C@@H](C)CC
  • InChI=1S/C27H31I2NO5/c1-5-17(4)34-24(31)16-23-25(19-10-8-9-11-22(19)35-23)26(32)18-14-20(28)27(21(29)15-18)33-13-12-30(6-2)7-3/h8-11,14-15,17H,5-7,12-13,16H2,1-4H3/t17-/m0/s1
  • Key:ZXOSVKYCXLTVGS-KRWDZBQOSA-N

Budiodarone (ATI-2042) is an

clinical trials. Amiodarone is considered the most effective antiarrhythmic drug available,[1][2][3] but its adverse side effects, including hepatic, pulmonary and thyroid toxicity as well as multiple drug interactions,[4] are discouraging its use. Budiodarone only differs in structure from amiodarone through the presence of a sec-butyl acetate side chain at position 2 of the benzofuran moiety.[5] This side chain allows for budiodarone to have a shorter half-life in the body than amiodarone (7 hours versus 35–68 days) which allows it to have a faster onset of action and metabolism while still maintaining similar electrophysiological activity.[4]
The faster metabolism of budiodarone allows for fewer adverse side effects than amiodarone principally due to decreased levels of toxicity in the body.

Creation of arrythmias

atrial myocytes. Arrhythmias have historically been treated using atrial ablation
or antiarrhythmic drugs to decrease electrical re-entry and therefore fibrillation.

Treatment of arrhythmias

Budiodarone holds much promise as an antiarrhythmic drug to prevent fibrillation. As a drug that spans over many of antiarrhythmic drug classes, the electrophysiological activity of budiodarone includes:[4]

Inhibition of potassium, sodium and calcium channels

Through inhibiting potassium channels, budiodarone causes a decreased efflux of potassium out of the myocyte during the refractory period of its action potential, increasing the time it takes to reach the resting membrane potential.

Through blocking sodium channels, budiodarone causes a decrease in sodium influx into myocytes during the depolarization period of its action potential.

Through blocking calcium channels, budiodarone causes a decrease in calcium influx into myocytes, decreasing intracellular calcium and decreasing cardiac contractility, which is beneficial in preventing arrhythmias, but detrimental in ventricular contraction.

Increase in atrial myocyte refractory period

Through prolonging the refractory and depolarization periods of the action potential, there is a decreased likelihood that electrical re-entry will occur.

Increased stimulus-to-atrium and atrium-to-bundle of his intervals

Increasing the time interval between stimulus to atrium and/or atrium to

bundle of his
in action potential conduction slows the rate of myocyte contraction, thereby slowing heart rate.

Increased MAPD90 and QT-intervals

Increasing the time interval of MAPD90 (response of monophasic action potential duration at 90% repolarization)in action potential conduction, slowing the rate of myocyte contraction, thereby slowing heart rate.

Dose-dependent decrease in heart rate

A decrease in heart rate reduces the risk of atrial fibrillation.

Clinical trials

Preliminary trials of budiodarone have administered the drug orally as a

bid doses were associated with the highest reduction in atrial fibrillation burden (54.4% and 75% respectively)[8] while remaining free of the adverse side effects common with amiodarone.[7] In addition to reductions in atrial fibrillation burden, similar dose-dependent reductions in the number of atrial fibrillation episodes and the duration of atrial fibrillation episodes have been demonstrated. [7][8]

There has also been evidence of prolonged budiodarone cardiac effect days after drug discontinuation as the atrial fibrillation baseline measurements were not reached in washout periods.[7] This suggests that budiodarone may promote atrial re-modelling to improve malfunctioning ion channels that once potentiated fibrillation.

Future use

Data on the effects of long-term budiodarone are not yet available. The completion of current clinical trials will examine chronic budiodarone use to confirm or deny its use as an effective and safe antiarrhythmic drug.

See also

References

  1. PMID 10738049
    .
  2. PMID 15872201
    .
  3. PMID 10956284
    .
  4. ^
    PMID 11259553
    .
  5. CiteSeerX 10.1.1.991.2904
    .
  6. PMID 12062331
    .
  7. ^
    PMID 19174378
    .
  8. ^ a b c Ezekowitz M, Hohnloser SH, Lubinski A, Bandman O, Canafax D, Ellis DJ, Milner PG, Ziola M, Thibault B (May 2009). PASCAL: a randomized doubleblind, placebo-controlled study of budiodarone (ATI-2042) in patients with paroxysmal atrial fibrillation and pacemakers with atrial fibrillation data logging capabilities. Heart Rhythm Society Annual Scientific Sessions. Boston, Mass.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Budiodarone&oldid=1203337898"