A tryptamine analog with high affinity to the heart tissues is a potential antiarrhythmic agent.
A novel tryptamine analog, 1-methyl-3-[N-(3-indolyl)ethyl]carbamoyl-1,4-dihydropyridine (T-CDS) was synthesized and converted into a stable, solid complex with 2-hydroxypropyl-beta-cyclodextrin. An aqueous solution of the complex was given intravenously to dogs and the concentration of T-CDS and its corresponding quaternary (T-Q+) forms were monitored in the blood for 50 min. The effect of the drug on vital heart parameters was monitored throughout the studies. At the end of the experiment the dogs were sacrificed and the concentration of the quaternary pyridinium form (T-Q+) was determined in the different heart tissues, as well as in the kidney, liver, lung, brain, urine and cerebrospinal fluid. The compound was found to be selectively bound to the heart muscles and showed different concentrations in different heart tissues. The T-Q+ concentrations were much higher in the heart after administration of the dihydro form (T-CDS), than after administering T-Q+ directly. The compound was found to be active on certain vital signs of the cardiovascular system and could be an effective and safe antiarrhythmic agent.
Bodor
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Center for Drug Discovery, University of Florida, Gainesville 32610-0497, USA.
Farag
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Polgar
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001665:Binding Sites; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D007262:Infusions, Intravenous; D008297:Male; D009206:Myocardium / Q000737:chemistry*; D014018:Tissue Distribution; D014363:Tryptamines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D014363:Tryptamines