Table 1

Potencies of 3α-diphenylmethoxytropane analogs in binding to the dopamine transporter1-a and M1 muscarinic receptors, inhibiting dopamine uptake1-a, and in effecting locomotor activity1-b

CompoundDopamine Transporter KiValue1-a (% error)Uptake Inhibition IC50Value1-a (±S.E.M.)M1Ki Value (% error)Locomotor Activity ED50 Value1-b and 95% Confidence LimitsLocomotor Activity Maximum Stimulation1-c(±S.E.M.)
nM nM nM μmol/kg counts/30 min
Cocaine15.6 (1)15,193
12.1–19.6(±829)
BZT1184032.14.96 (4)9,521
(9)(±115)(14)2.48–9.89(±1,561)
4′-F-BZT32.2485.27.88 (4)10,223
(10)(±13)(8)5.61–11.0(±1,409)
4′,4"-diF-BZT11.871912.1 (4)12,449
(11)(±12)(10)9.77–14.9(±974)
3′,4′-diCl,4"-F-BZT18.923.938.914.8 (4)9,322
(14)(±14.7)(9)8.80–24.8(±1,771)
3′,4′-diF-BZT27.91813.797.45 (4)11,604
(11)(±45.6)(9)4.58–12.1(±976)
3′,4"-diF-BZT23.31395.87 268 (1)n.s.
(8)(±23.8)(9) 126–576
4′-Br,4"-F-BZT15.227.222.410.4 (4)10,577
(19)(±14.7)(9)8.24–13.1351
4′-Cl-BZT30.01154.39.65 (3)7,770
(12)(±27.6)(9)5.39–17.3(±871)
4′-Cl-BZT (β)854352018.9 66.1 (1)n.s.
(7)(±1,010)(9) 41.9–105
4′,4"-diCl-BZT20.07540.66.98 (4)5,495
(14)(±24)(8)2.96–16.5(±473)
3′,4′-diCl-BZT21.146.714.713.1 (4)9,062
(19)(±14.5)(11)9.40–18.1(±2,082)
4′-Br-BZT37.928.66.2420.3 (4)8,175
(7)(±15.5)(10)12.2–33.9(±1,460)
4′,4"-diBr-BZT91.634.385.1 17.0 (1)n.s.
(13)(±13.7)(10) 13.6–21.4
4′-CH3-BZT18751211.6 57.3 (1)n.s.
(5)(±121)(9) 39.5–84.4
4′-CN-BZT19622222.04.50 (4)2,907
(9)(±55.2)(6)3.61–6.38(±587)
4′-OH-BZT2976778.54 67.7 1-d (1)n.s.
(13)(±164)(7) 47.5–96.6
4′-CF3-BZT6352,16027.6 40.6 1-d (1)n.s.
(10)(±710)(8) 35.2–54.7
4′-OMe-BZT78.446812.2 63.7 (1) n.s.
(8)(±114)(8) 53.3–75.3
4′,4"-diOMe-BZT20002880120 48.7 (1)n.s.
(7)(±956)(5) 40.5–58.6
  • 1-a Some of these values have been reported previously (Newman et al., 1995).

  • 1-b ED50 values depicted with a normal font are for stimulation of locomotor activity, those depicted with italics are for the LMA depressant effects of compounds that did not significantly stimulate activity. The number in parentheses following the ED50 value indicates which 30-min period following injection from which these data were collected and in which the maximal effect was obtained. With data collected in successive 10-min epochs, there were four partially overlapping 30-min periods from which the data were selected.

  • 1-c For those compounds that did not significantly stimulate activity, not significant (n.s.) is placed in the last column rather than a value representing maximal stimulant efficacy. The ED50values were calculated as described in Methods.

  • 1-d ED50 value is only an estimate because there was a significant deviation from linearity.