Non-amine-based dopamine transporter (reuptake) inhibitors retain properties of amine-based progenitors.
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.
Madras
Bertha K
BK
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
Fahey
Michele A
MA
Miller
Gregory M
GM
De La Garza
Richard
R
Goulet
Martin
M
Spealman
Roger D
RD
Meltzer
Peter C
PC
George
Susan R
SR
O'Dowd
Brian F
BF
Bonab
Ali A
AA
Livni
Eli
E
Fischman
Alan J
AJ
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
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