RT Journal Article
SR Electronic
T1 Structural Characteristics for Inhibition of [<sup>3</sup>H] Norepinephrine Uptake into Rat Brain Synaptic Vesicles by Beta-Carboline, Indolealkylamine, Phenethylamine and <em>n</em>-Alkylamine Derivatives
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 607
OP 619
VO 15
IS 3
A1 SLOTKIN, THEODORE A.
A1 SALVAGGIO, MARIA
A1 SEIDLER, FREDERIC J.
A1 WHITMORE, WILLIAM L.
YR 1979
UL http://molpharm.aspetjournals.org/content/15/3/607.abstract
AB The abilities of four different classes of monoamines to inhibit uptake of [3H]norepinephrine into rat brain synaptic vesicles were evaluated. Compounds from all four produced competitive inhibition with the following general order of potency: β-carbolines&gt; indolealkylamines&gt; phenalkylamines&gt; n-alkylamines. The minimal structural features required for uptake inhibition consisted of an amino nitrogen separated from a hydrophobic moiety by at least a 2-carbon bridge. The most important substituent group was the 5-hydroxyl group for indolealkylamines, the p-hydroxyl group for the phenalkylamines or the 7-methoxyl group for the β-carbolines. Linear alkylamines produced a dual effect, with competitive inhibition of uptake at low concentrations and detergent-like actions predominating with increasing chain length or with high concentrations. Analysis of the details of structure-activity relationships indicates that the characteristic of the amine transport site of brain catecholamine vesicles differs substantially from that of adrenomedullary vesicles. ACKNOWLEDGMENTS The authors thank Gloria Barnes, Christopher Lau and Brian McTier for their assistance.