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

P R Carlier; M M Lo; P C Lo; E Richelson; M Tatsumi; I J Reynolds; T A Sharma

doi:10.1016/s0960-894x(98)00062-6

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

Bioorg Med Chem Lett. 1998 Mar 3;8(5):487-92. doi: 10.1016/s0960-894x(98)00062-6.

Authors

P R Carlier¹, M M Lo, P C Lo, E Richelson, M Tatsumi, I J Reynolds, T A Sharma

Affiliation

¹ Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.

PMID: 9871604
DOI: 10.1016/s0960-894x(98)00062-6

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Alcohols / chemistry*
Animals
Antidepressive Agents / chemical synthesis*
Antidepressive Agents / chemistry
Antidepressive Agents / pharmacology
Dopamine / metabolism*
Humans
Neurotransmitter Uptake Inhibitors / chemical synthesis*
Neurotransmitter Uptake Inhibitors / chemistry
Neurotransmitter Uptake Inhibitors / pharmacology
Norepinephrine / metabolism*
Rats
Serotonin / metabolism*
Species Specificity

Substances

Amino Alcohols
Antidepressive Agents
Neurotransmitter Uptake Inhibitors
Serotonin
Dopamine
Norepinephrine

Grants and funding

DA07490/DA/NIDA NIH HHS/United States