Drug | Monoamine Uptake (Ki) | Microdialysis | ||||||
---|---|---|---|---|---|---|---|---|
[3H]DA | [3H]NE | [3H]5-HT | [3H]DA | [3H]NE | [3H]5-HT | |||
nM | % | μM | ||||||
BTS 74 398 | 4.2 | 6.9 | 19a | n/a | n/a | n/a | n/a | n/a |
GBR 12909 | 42 | 624 | 480 # | 51 | 2,600 | n/ab | 691 | 100e |
Bupropion | 409 | 2,590 | 18,312a | 630 | 2,300 | 15,600c | 742 | 1,000e |
Nomifensine | 88 | 8.0 | 2,660a | 51 | 5.0 | 1,280c | 2,117 | 1,000e |
Nisoxetine | 279 | 2.1 | 296 # | 510 | 1.3 | 310c | ||
Sertraline | 101 | 2,763 | 2.8 # | 1.1 | 1.2 | 0.058d |
[3H]Monoamine uptake by BTS 74 398 and other reuptake inhibitors was determined from rat striatal (DA) or cortical (NE and 5-HT) synaptosomal preparations, as described in Cheetham et al. 1998(a) or unpublished observations (S. C. Cheetham, S. Butler, N. Slater, J. Viggers, and D. J. Heal) ( #) performed under identical conditions. Data are the mean of three to four experiments and agree with previously published, mean inhibitory constants (IC i50), Richelson and Pfenning (1984) (c), and Koe et al. (1983)(d; IC50). Also provided are the relative in vivo potency of these compounds to increase rat striatal DA levels, taken from the microdialysis study of Nomikos et al (1990)(e), using awake and freely moving rats. Striatal DA levels are expressed as a mean percentage increase from baseline DA level (n = 3–4) after local infusion of drug at specified concentration (micromolar).
n/a, data not available.