TY - JOUR
T1 - Vesicular monoamine transporter 2
T2 - Role as a novel target for drug development
AU - Zheng, Guangrong
AU - Dwoskin, Linda P.
AU - Crooks, Peter A.
PY - 2006/11/10
Y1 - 2006/11/10
N2 - In the central nervous system, vesicular monoamine transporter 2 (VMAT2) is the only transporter that moves cytoplasmic dopamine (DA) into synaptic vesicles for storage and subsequent exocytotic release. Pharmacologically enhancing DA sequestration by VMAT2, and thus preventing the oxidation of DA in the cytoplasm, may be a strategy for treating diseases such as Parkinson's disease. VMAT2 may also be a novel target for the development of treatments for psychostimulant abuse. This review summarizes the possible role of VMAT2 as a therapeutic target, VMAT2 ligands, reported in the literature, and the structure-activity relationship of these ligands, including tetrabenazine analogs, ketanserin analogs, lobeline analogs, and 3-amine-2-phenylpropene analogs. The molecular structure of VMAT2 and its relevance to ligand binding are briefly discussed.
AB - In the central nervous system, vesicular monoamine transporter 2 (VMAT2) is the only transporter that moves cytoplasmic dopamine (DA) into synaptic vesicles for storage and subsequent exocytotic release. Pharmacologically enhancing DA sequestration by VMAT2, and thus preventing the oxidation of DA in the cytoplasm, may be a strategy for treating diseases such as Parkinson's disease. VMAT2 may also be a novel target for the development of treatments for psychostimulant abuse. This review summarizes the possible role of VMAT2 as a therapeutic target, VMAT2 ligands, reported in the literature, and the structure-activity relationship of these ligands, including tetrabenazine analogs, ketanserin analogs, lobeline analogs, and 3-amine-2-phenylpropene analogs. The molecular structure of VMAT2 and its relevance to ligand binding are briefly discussed.
KW - Ketanserin
KW - Lobeline
KW - Parkinson's disease
KW - Psychostimulant abuse
KW - Tetrabenazine
KW - Vesicular monoamine transporter 2
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U2 - 10.1208/aapsj080478
DO - 10.1208/aapsj080478
M3 - Review article
C2 - 17233532
AN - SCOPUS:33751242500
SN - 1550-7416
VL - 8
JO - AAPS Journal
JF - AAPS Journal
IS - 4
M1 - 78
ER -