GLPG0634 ANALOGUE

IC50: 12 nM (serotonin), 23 nM (norepinephrine), 96 nM (dopamine).

Amitifadine (DOV 21,947) is an antidepressant drug. K _i values for SERT, NET, and DAT are 99 nM, 262 nM, and 213 nM. The IC ₅₀ values for serotonin, norepinephrine and dopamine uptake are 12, 23 and 96 nM, respectively.

The 30 mg/kg Amitifadine dose significantly reduces nicotine self-administration. The 5 and 10 mg/kg doses reduce nicotine self-administration during the first 15 min. of the session when the greatest amount of nicotine is self-administered. The 30 mg/kg Amitifadine dose, but not the lower doses cause a significant reduction in locomotor activity averaged over the 1-hour session and reduce food motivated responding. The 10 mg/kg dose causes hypoactivity at the beginning of the session, but 5 mg/kg does not cause any hypoactivity. The effect of chronic Amitifadine treatment (10 mg/kg) over the course of 15 sessions is also determined. Amitifadine causes a significant reduction in nicotine self-administration, which is not seen to diminish over two consecutive weeks of treatment and a week after enforced abstinence. Amitifadine significantly reduces nicotine self-administration. This prompts further research to determine if Amitifadine might be an effective treatment for smoking cessation.