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| Pronunciation | (/æmɪˈtɪfədiːn/am-i-TIF-ə-deen) |
| Other names | DOV-21,947; EB-1010 |
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| Formula | C11H11Cl2N |
| Molar mass | 228.12 g·mol−1 |
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Amitifadine (developmental code namesDOV-21,947,EB-1010) is aserotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) or so-called triple reuptake inhibitor (TRI) which is or was being developed byEuthymics Bioscience.[1][2] It was under development for the treatment ofmajor depressive disorder, but in May 2013, it was reported that the drug failed to show superiorefficacy toplacebo in aphase IIb/IIIaclinical trial.[3] it was suggested that this may have been due to the drug being underdosed.[3] In September 2017, development of amitifadine for the treatment of major depressive disorder was finally officially discontinued.[1] As of September 2017, it is still listed as being under development for the treatment ofalcoholism andsmoking withdrawal.[1]
Ki values forSERT,NET, andDAT of amitifadine are 99 nM, 262 nM, and 213 nM.[2] TheIC50 values forserotonin,norepinephrine anddopamine uptake are 12, 23 and 96 nM, respectively.
| Compound | Uptake (IC50, nM) | Binding (Ki, nM) | ||||
|---|---|---|---|---|---|---|
| 5-HT | NE | DA | SERT | NET | DAT | |
| Amitifadine | 12 | 23 | 96 | 100 | 260 | 210 |
| DOV-216,303 | 14 | 20 | 78 | 190 | 380 | 190 |
| DOV-102,677 | 130 | 100 | 130 | 740 | 1000 | 220 |
Amitifadine reduces the duration of immobility in theforced swim test in rats with an oralminimum effective dose (MED) of 5 mg/kg. This antidepressant-like effect manifests in the absence of significant increases in motor activity at doses of up to 20 mg/kg. Amitifadine also produces a dose-dependent reduction in immobility in thetail suspension test, with an oral MED of 5 mg/kg. In microdialysis studies, amitifadine increased extracellular levels of serotonin, norepinephrine and dopamine in brain regions and did not induce hyperactivity in rats.[4]Results in a small clinical trial indicated that amitifadine had statistically significant antidepressant effects and was well tolerated.[5]
Amitifadine is the (+)-enantiomer ofDOV-216,303, and its (−)-enantiomer isDOV-102,677.
Amitifadine is very similar in structure tobicifadine andcentanafadine.
A so-called "bifunctional molecule" from a separate organization calledGSK 598809 has related structure.
