Journal of Pharmacy and Pharmacology JPP 2001, 53: 889–894  2001 The Authors Received February 2, 2001 Accepted March 9, 2001 ISSN 0022-3573 A tryptamine analog with high affinity to the heart tissues is a potential antiarrhythmic agent Nicholas Bodor, Hassan H. Farag and Peter Polgar Abstract 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-β- 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. Introduction Tryptamine (T, 1 ; Figure 1) is an indolealkylamine which is biosynthetically derived from the essential amino acid tryptophan. Tryptamine is present in very low endogenous concentrations. The application of a redox targeting system for enhanced brain-targeted delivery of this amine, based on the 1,4-dihydrotrio- nelline  trigonelline redox pair was previously reported (Bodor et al 1986). Briefly, tryptamine is converted into its corresponding trigonellylamide (T-Q + , 3), which is reduced to the 1,4-dihydrotrigonellylamide derivative, which is called a chemical delivery system (T-CDS, 4). When administered intravenously to animals, it was shown that the lipophilic T-CDS is distributed throughout the body, including the brain, followed by enzymatic oxidative conversion by the ubiquitous NAD +  NADH coenzyme system, into the hydrophilic T-Q + . This, in turn, is quickly eliminated from the body, but the portion formed in the brain is locked-in by the blood–brain barrier, providing a long-term presence of T-Q + , which subsequently is slowly cleaved to tryptamine, providing its sustained release. This redox system was shown to provide enhanced and targeted delivery of various therapeutic agents to the CNS in a specific and sustained fashion (Bodor et al 1981 ; Bodor & Buchwald 1999). Examples include dopamine (Bodor & Farag 1983; Simpkins et al 1985; Omar et al 1994), estradiol (Bodor et al 1987; Simpkins et al 1986 ; Estes et al 1987), penicillins (Pop et al 1989), antiepileptics Center for Drug Discovery, University of Florida, PO Box 100497, JHMHC, Gainesville, Florida 32610-0497, USA Nicholas Bodor Faculty of Pharmacy, University of Assiut, Egypt Hassan H. Farag Medical University of Debrecen, Debrecen, Hungary Peter Polgar Correspondence : N. Bodor, Center for Drug Discovery, University of Florida, PO Box 100497, JHMHC, Gainesville, Florida 32610-0497, USA. 889