TABLE 4

In vitro pharmacological profile of HTBZ isomers

Dopamine, serotonin, and adrenergic receptors were assessed through radioligand binding, and monoamine transport sites were assessed through radioligand uptake. All assays were performed in two independent experiments and in triplicate. Where the Ki values were below 500 nM, assays were performed in 3–5 independent experiments.

TargetR,R,R-HTBZaS,R,R-HTBZS,S,S-HTBZR,S,S-HTBZ
Ki, nMpKi Mean (S.D.)bnKi, nMpKi Mean (S.D.)bnKi, nMpKi Mean (S.D.)bnKi, nMpKi Mean (S.D.)bn
VMAT24.28.38 (0.42)279.78.01 (0.32)62506.60 (0.22)46906.16 (0.05)5
Dopamine D1>5000<52>5000<52>5000<5240005.40 (0.05)2
Dopamine D2(s)>5000<52>5000<521806.73 (0.23)5537.27 (0.18)6
Serotonin 5-HT1A61005.21 (0.07)275005.13 (0.05)27506.13 (0.23)215005.82 (0.41)2
Serotonin 5-HT2A>5000<52>5000<52>5000<5222005.66 (0.00)2
Serotonin 5-HT2B>5000<52>5000<526006.22 (0.33)34606.34 (0.40)4
Serotonin 5-HT7>5000<529706.01 (0.03)2717.15 (0.12)25.98.23 (0.08)2
α1A Adrenergic>5000<52>5000<52>5000<529806.01 (0.15)4
α2A Adrenergic>5000<52>5000<5217005.76 (0.08)22206.65 (0.36)2
DAT>5000<52>5000<52>5000<52>5000<52
NET>5000<5292005.03 (0.00)295005.02 (0.00)2>5000<52
SERT>5000<52>5000<52>5000<52>5000<52
  • DAT, dopamine transporter; NET, norepinephrine transporter; SERT, serotonin transporter.

  • a Major metabolite of VBZ.

  • b pKi is the negative logarithm of Ki. S.D. are only presented for pKi values >5.