PMID- 7550031
OWN - NLM
STAT- MEDLINE
DCOM- 19951030
LR  - 20190920
IS  - 0969-8051 (Print)
IS  - 0969-8051 (Linking)
VI  - 22
IP  - 4
DP  - 1995 May
TI  - Amino- and amido-tetrabenazine derivatives: synthesis and evaluation as potential 
      ligands for the vesicular monoamine transporter.
PG  - 527-35
AB  - Tetrabenazine (TBZ) and dihydrotetrabenazine are well known inhibitors of the CNS 
      vesicular monoamine transporter (VMAT), which is responsible for the packaging of 
      monoamine neurotransmitters in presynaptic vesicles. Amino and amido derivatives 
      of tetrabenazine were prepared as potential ligands for the vesicular monoamine 
      transporter. Ultimately, organotin derivatives of promising ligands were prepared 
      for radiolabeling with 125I. The compounds were evaluated for their ability to 
      inhibit the specific binding of a selective radioligand to the transporter in rat 
      striatal homogenates. Of the compounds evaluated, three amine derivatives of TBZ 
      (primary, secondary and tertiary) were found to have modest to high affinity for 
      the transporter, while two amides exhibited low to undectable affinity. The 
      secondary propargyl amine was found to possess the highest affinity (Ki = 7.6 nM) 
      and was chosen for further evaluation. The organotin derivative of this compound 
      was synthesized in order to prepare the corresponding radioiodinated ligand. 
      However, our inability to synthesize and characterize the iodinated amine 
      precluded its evaluation as a potential radioiodinated ligand for the 
      transporter. Alternative approaches for decreasing the lipophilicity of TBZ 
      analogs while maintaining high binding affinity are currently being explored.
FAU - Canney, D J
AU  - Canney DJ
AD  - Department of Radiology, University of Pennsylvania, Philadelphia 19104, USA.
FAU - Kung, M P
AU  - Kung MP
FAU - Kung, H F
AU  - Kung HF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nucl Med Biol
JT  - Nuclear medicine and biology
JID - 9304420
RN  - 0 (Amides)
RN  - 0 (Amines)
RN  - 0 (Glycoproteins)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Vesicular Biogenic Amine Transport Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - Z9O08YRN8O (Tetrabenazine)
SB  - IM
MH  - Amides
MH  - Amines
MH  - Animals
MH  - Cell Membrane/metabolism
MH  - Corpus Striatum/*metabolism
MH  - Glycoproteins/analysis/*metabolism
MH  - Indicators and Reagents
MH  - *Iodine Radioisotopes/metabolism
MH  - Isotope Labeling/methods
MH  - Magnetic Resonance Spectroscopy
MH  - *Membrane Glycoproteins
MH  - *Membrane Transport Proteins
MH  - Molecular Structure
MH  - *Neuropeptides
MH  - Neurotransmitter Agents/metabolism
MH  - Radioligand Assay
MH  - Rats
MH  - Tetrabenazine/*analogs & derivatives/chemical synthesis/*metabolism
MH  - Vesicular Biogenic Amine Transport Proteins
MH  - Vesicular Monoamine Transport Proteins
EDAT- 1995/05/01 00:00
MHDA- 1995/05/01 00:01
CRDT- 1995/05/01 00:00
PHST- 1995/05/01 00:00 [pubmed]
PHST- 1995/05/01 00:01 [medline]
PHST- 1995/05/01 00:00 [entrez]
AID - 0969-8051(94)00118-4 [pii]
AID - 10.1016/0969-8051(94)00118-4 [doi]
PST - ppublish
SO  - Nucl Med Biol. 1995 May;22(4):527-35. doi: 10.1016/0969-8051(94)00118-4.