Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group.
A series of gamma-amino alcohols were synthesized and screened for reuptake inhibition and noncompetitive NMDA antagonism. Compound (+/-)-3f simultaneously and potently inhibits reuptake of 5-HT, NE, and DA, representing a potential wide-spectrum reuptake inhibitor antidepressant. In addition, comparative rat and human studies uncovered a species-selective DA reuptake inhibitor (+/-)-2e, KD(hDAT)/KD(rDAT) = 97.
Carlier
P R
PR
Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Lo
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MM
Lo
P C
PC
Richelson
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Tatsumi
M
M
Reynolds
I J
IJ
Sharma
T A
TA
D000605:Amino Alcohols / Q000737:chemistry*; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D014179:Neurotransmitter Uptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013045:Species Specificity
D000605:Amino Alcohols; D000928:Antidepressive Agents; D014179:Neurotransmitter Uptake Inhibitors; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine