TABLE 1

Comparison of VU0134992 and antidepressant selectivity for Kir4.1 over other Kir channels

Data shown are mean IC50 micromolar values and maximal percentage inhibition at 30 and 90 ยตM in parentheses derived from Tl+ flux assays. Experiments were performed in triplicate on 2 separate days.

ChannelVU0134992AmitriptylineNortriptylineFluoxetine
Kir1.1Inactive33.0 (16%, 58%)31.0 (6%, 50%)27.0 (6%, 30%)
Kir2.1Inactive35.0 (1%, 36%)Inactive10.1 (10%, 86%)
Kir2.2Inactive41.7 (2%, 41%)InactiveInactive
Kir2.313.2 (73%)21.3 (53%, 89%)19.4 (60%, 91%)7.1 (98%, 100%)
Kir3.1/3.22.5 (92%)13.6 (73%, 91%)16.1 (65%, 87%)3.4 (97%, 100%)
Kir3.1/3.43.1 (92%)12.0 (67%, 88%)15.0 (56%, 80%)2.4 (94%, 100%)
Kir4.15.2 (100%)89.0 (0%, 66%)41.7 (10%, 93%)31.2 (35%, 95%)
Kir4.28.1 (100%)42.7 (0%, 45%)46.7 (0%, 65%)20.2 (98%, 99%)
Kir6.2/SUR111.4 (12%)32.2 (4%, 64%)42.0 (0%, 52%)64 (4%, 65%)
Kir7.134.2 (15%)22.9 (65%, 89%)26.0 (50%, 82%)5.8 (75%, 92%)