title: Non-amine-based dopamine transporter (reuptake) inhibitors retain properties of amine-based progenitors.
abstract: Without exception, therapeutic and addictive drugs that produce their primary effects by blocking monoamine transporters in brain contain an amine nitrogen in their structure. This fundamental canon of drug design was based on a prevailing premise that an amine nitrogen is required to mimic the structures of monoamine neurotransmitters and other natural products. Non-amines, a novel class of compounds that contain no amine nitrogen, block monoamine transporters in the nM range and display markedly high selectivity for monoamine transporters, but not for receptors. Non-amines retain the spectrum of biochemical and pharmacological properties characteristic of amine-bearing counterparts. These novel drugs compel a revision of current concepts of drug-monoamine transporter complex formation and open avenues for discovery of a new generation of therapeutic drugs.
authors: Department of Psychiatry, Harvard Medical School, New England Primate Research Center, 1 Pine Hill Drive, Southborough, MA 01772-9102, USA. bertha_madras@hms.harvard.edu
authors: Bertha K
authors: BK
authors: Madras
authors: Michele A
authors: MA
authors: Fahey
authors: Gregory M
authors: GM
authors: Miller
authors: Richard
authors: R
authors: De La Garza
authors: Martin
authors: M
authors: Goulet
authors: Roger D
authors: RD
authors: Spealman
authors: Peter C
authors: PC
authors: Meltzer
authors: Susan R
authors: SR
authors: George
authors: Brian F
authors: BF
authors: O'Dowd
authors: Ali A
authors: AA
authors: Bonab
authors: Eli
authors: E
authors: Livni
authors: Alan J
authors: AJ
authors: Fischman
mesh_terms: D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012453:Saimiri; D013329:Structure-Activity Relationship
chemical_list: D001679:Biogenic Amines; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins