Tetrabenazine

Tetrabenazine (Ro 1-9569) is a brain-penetrant and orally active VMAT2-selective ligand with human VMAT2 K_i 100 nM. Tetrabenazine binds VMAT2 to block monoamine uptake into synaptic vesicles, potentiates cytoplasmic monoamine degradation. Tetrabenazine weakly blocks dopamine D2 receptors, and increases dopamine turnover via elevated cerebrospinal fluid homovanillic acid. Tetrabenazine can be used for the research of Huntington’s disease, tardive dyskinesia, and Tourette’s syndrome^[1][2][3]. In Vitro:Tetrabenazine reversibly inhibits human VMAT2 with a K_i of ~100 nM, reducing monoamine uptake into synaptic vesicles and depleting presynaptic monoamine stores^[1].
Tetrabenazine inhibits dopamine D2 receptors in striatal membranes with a K_i of ~2.1 μM^[1].
Tetrabenazine (0.3-10.0 μg/mL; 4 h) releases serotonin from rabbit blood platelets in vitro in a concentration-dependent manner^[3].
Tetrabenazine (5-20 mg/L) is 60% bound to nondiffusible components of rabbit plasma^[3]. In Vivo:Tetrabenazine provides partial neuroprotection in a transgenic HD mouse model of Glutamate-induced striatal neurodegeneration^[1].
Tetrabenazine (7 days) causes irreversible locomotor changes and substantia nigra pars compacta neuronal damage in healthy rats^[1].
Tetrabenazine (50-150 mg/kg; i.v.; daily for 3-9 days) exhibits short-lived, central nervous system-selective Reserpine (HY-N0480)-like effects in rabbits^[3].