RT Journal Article SR Electronic T1 Isomers of 2,4,5-Trihydroxyphenethylamine (6-Hydroxydopamine): Long-Term Effects on the Accumulation of [3H]-Norepinephrine in Mouse Heart in Vivo JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 505 OP 513 VO 9 IS 4 A1 J. LUNDSTROM A1 H. ONG A1 J. DALY A1 C. R. CREVELING YR 1973 UL http://molpharm.aspetjournals.org/content/9/4/505.abstract AB The immediate and long-term effects of the six isomeric trihydroxyphenethylamines and 2,3,4,5-tetrahydroxyphenethylamine on the uptake and release of [3H]norepinephrine from storage sites in cardiac tissue of the mouse in vivo have been compared. In addition, the rate of autoxidation of these amines has been measured. The order of potency of the various isomers for inhibition of uptake is: 3,4,5 = 2,4,5 = 2,3,4 > 2,3,4,5 > 2,3,5 >> 2,4,6 > 2,3,6; the order of activity for release is: 2,4,5 = 3,4,5 > 2,3,5 > 2,3,4 > 2,3,4,5 >> 2,4,6 >> 2,3,6. The α-methyl derivative of the 2,4,5-isomer (6-hydroxydopamine) is nearly twice as effective as the parent amine as a releasing agent , while the N,N-dimethyl derivative is completely inactive. The order for rate of autoxidation is: 2,3,4,5 >> 2,3,5 = 2,3,6 = 2,4,5 = N,N-dimethyl-2,4,5 > 2,3,4 > 3,4,5 >> 2,4,6. Only the 2,4,5-isomer, the α-methyl derivative of the 2,4,5-isomer, the 2,3,5-isomer, and the 2,3,4,5-tetrahydroxyphenethylamine cause long-term reduction in the cardiac uptake of [3H]norepinephrine. These results support the hypothesis that neurodegeneration can only be initiated when a critical intraneuronal concentration of a readily autoxidizable amine is attained as a direct result of an affinity of the amine for the active uptake process at the neuronal membrane. ACKNOWLEDGMENT The authors wish to acknowledge the expert technical assistance of Ms. Elizabeth McNeal.