RT Journal Article SR Electronic T1 Dihydroxytryptamines: Effects on Noradrenergic Function in Mouse Heart in Vivo JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 211 OP 222 VO 11 IS 2 A1 C. R. CREVELING A1 J. LUNDSTROM A1 E. T. McNEAL. A1 L. TICE A1 J. W. DALY YR 1975 UL http://molpharm.aspetjournals.org/content/11/2/211.abstract AB A variety of tryptamines, including the four isomeric hydroxytryptamines and four isomeric dihydroxytryptamines, inhibit uptake of [3H]norepinephrine into mouse heart in vivo and elicit release of [3H]norepinephrine from cardiac storage sites. α-Methyl congeners are more potent releasing agents, except in monoamine oxidase-inhibited mice, where in most cases the parent amines become almost as efficacious. Only 5.7-dihydroxytryptamine and, to a lesser extent, 6,7-dihydroxytryptamine have longterm cytotoxic effects on noradrenergic terminals in heart, as evident in a marked reduction in uptake of [3H]norepinephrine for 5-20 days after exposure to the amines and, for the 5,7-hydroxy-analog, in degenerative changes in the ultrastructure of atrial nerves. Cocaine prevents both [3H]norepinephrine release and the long-term effects of 5,7-dihydroxytryptamine. α-Methyl-5,7dihydroxytryptamine does not elicit any long-term effects, nor does the parent amine in animals in which monoamine oxidase has been inhibited. Dihydroxytryptamines undergo autoxidation much more slowly than cytotoxic phenethylamines, such as 6-hydroxy-dopamine, which are autoxidized rapidly. The mechanism involved in the cytotoxic effects of 5,7-dihydroxytryptamine in heart tissue thus contrasts in many aspects with that involved in the action of 6-hydroxy-dopamine. ACKNOWLEDGMENT The authors wish to acknowledge the capable assistance of Mrs. M. Cahill.