Table 4.
Interaction of Mefloquine and other drugs with recombinant human neurotransmitter transporters
| Dopamine transporter | Norepinephrine transporter | Serotonin transporter | |
|---|---|---|---|
| Drug | A. Inhibition of [125I]RTI-55 binding | ||
| Ki (nM) ± SEM | |||
| (+)-Mefloquine | >6,400# | 5,300 ± 710 | 229 ± 39 |
| (−)-Mefloquine | 6,500 ± 930 | 5,280 ± 59 | 2,900 ± 310 |
| Chloroquine | >8,000# | 1,052 ± 81 | >8,300# |
| Quinine | >8,300# | >5,500# | >4,000# |
| LSD | >10 μM | 5,600 ± 260 | >10 μM |
| Cocaine | 416 ± 59 | 410 ± 120 | 450 ± 140 |
|
| |||
| Drug | B. Inhibition of [3H] neurotransmitter uptake | ||
| IC50 (nM) ± SEM | |||
| (+)Mefloquine | >10 μM | >10 μM | 341 ± 64 |
| (−)Mefloquine | >10 μM | >10 μM | >6,500# |
| Chloroquine | >10 μM | >10 μM | >10 μM |
| Quinine | >10 μM | >10 μM | 1,650 ± 420 |
| LSD | >10 μM | >10 μM | >10 μM |
| Cocaine | 272 ± 71 | 194 ± 21 | 295 ± 44 |
Specific [125I]RTI-55 binding to HEK-293 cells expressing each of the neurotransmitter transporters was assessed as described in the text. Each Ki value represents the mean of at least 3 independent experiments, each conducted with duplicate determinations. Cocaine, a neurotransmitter transporter blocker, was included for purposes of comparison.
If some experiments yielded IC50 or Ki values less than 10 μM and other experiments yielded IC50 or Ki values greater than 10 μM, the latter experiments were assigned a value of 10 μM and averages calculated. The actual value is greater than that average and no standard error is reported. Abbreviations: RTI-55 Methyl (1R,2S,3S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate; LSD lysergic acid diethylamide