[3H]methoxytetrabenazine: a high specific activity ligand for estimating monoaminergic neuronal integrity.

Abstract

The properties as well as the distribution of high specific activity alpha-[O-methyl-3H]methyoxytetrabenazine binding to the synaptic vesicular monoamine transporter were studied autoradiographically in rat brain sections. Saturation analysis revealed [3H]methoxytetrabenazine interaction with a homogeneous population of striatal sites (Hill coefficient 1.00 +/- 0.05), with an apparent equilibrium dissociation binding constant of 3.9 +/- 0.4 nM and a maximal binding capacity of 1.2 +/- 0.1 fmol/micrograms protein. Highest levels of [3H]methoxytetrabenazine binding sites were observed in regions richly innervated by the monoamine systems. In the presence of 1 microM concentrations of a variety of competing drugs, only reserpine significantly inhibited [3H]methoxytetrabenazine binding. The presynaptic nigrostriatal location of [3H]methoxytetrabenazine binding was demonstrated by unilateral lesion of the median forebrain bundle with 6-hydroxydopamine. The resulting decrease of striatal [3H]methoxytetrabenazine binding showed an excellent correlation with tyrosine hydroxylase-positive neuron density in the substantia nigra pars compacta (r2 = 0.96; P < 0.001). The present studies demonstrate that in vitro [3H]methoxytetrabenazine binding is a reliable, quantitative marker of the synaptic vesicular monoamine transporter. Further, it is indicated that [3H]methoxytetrabenazine binding provides an accurate assessment of monoamine neuronal losses and may thus be of great value in future studies of neurodegenerative diseases.

• Authors: T M Vander Borght, A A Sima, M R Kilbourn, T J Desmond, D E Kuhl, K A Frey
• Journal: Neuroscience (Neuroscience) Vol. 68 Issue 3 Pg. 955-62 (Oct 1995) ISSN: 0306-4522 [Print] United States
• PMID: 8577387 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biogenic Monoamines
• Ligands
• 5-O-methyldihydrotetrabenazine
• Oxidopamine
• Tyrosine 3-Monooxygenase
• Tetrabenazine

Topics

• Animals
• Autoradiography
• Binding, Competitive (drug effects)
• Biogenic Monoamines (physiology)
• Kinetics
• Ligands
• Medial Forebrain Bundle (cytology, enzymology, physiology)
• Neurons (drug effects)
• Oxidopamine (toxicity)
• Rats
• Tetrabenazine (analogs & derivatives)
• Tyrosine 3-Monooxygenase (metabolism)