Amitifadine

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Amitifadine
Amitifadine.svg
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Identifiers
CAS Number
PubChem CID
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UNII
KEGG
ChEMBL
Chemical and physical data
Formula C11H11Cl2N
Molar mass 228.118 g/mol
3D model (Jmol)
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Amitifadine (am-i-TIF-a-deen) (DOV-21,947 or EB-1010)[1] is an antidepressant drug being developed by Euthymics Bioscience Inc.[2] It is a so-called triple reuptake inhibitor (TRI) or serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI).[2]

It is the (+)-enantiomer of DOV-216,303, and its (−)-enantiomer is DOV-102,677. Ki values for SERT, NET, and DAT are 99 nM, 262 nM, and 213 nM.[2] The IC50 values for serotonin, norepinephrine and dopamine uptake are 12, 23 and 96 nM, respectively

DOV stereochemistry
DOV stereochemistry
Compound Uptake Binding
5-HT NE DA SERT NET DAT
DOV-216,303 14 20 78 190 380 190
Amitifadine 12 23 96 100 260 210
DOV-102,677 130 100 130 740 1000 220

Amitifadine reduces the duration of immobility in the forced swim test in rats with an oral minimum 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 the tail 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.[3] Results in a small clinical trial indicated that amitifadine had statistically significant antidepressant effects and was well tolerated.[4]

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References[edit]

  1. ^ "Amitifadine". AdisInsight. Retrieved 26 February 2017. 
  2. ^ a b c Skolnick, P.; Popik, P.; Janowsky, A.; Beer, B.; Lippa, A. S. (2003). "Antidepressant-like actions of DOV 21,947: a "triple" reuptake inhibitor". European Journal of Pharmacology. 461 (2–3): 99–104. doi:10.1016/S0014-2999(03)01310-4. PMID 12586204. 
  3. ^ Golembiowska, K.; Kowalska, M.; Bymaster, F. P. (2012). "Effects of the triple reuptake inhibitor amitifadine on extracellular levels of monoamines in rat brain regions and on locomotor activity". Synapse. 66 (5): 435–444. doi:10.1002/syn.21531. PMID 22213370. 
  4. ^ Tran, P.; Skolnick, P.; Czobor, P.; Huang, N. Y.; Bradshaw, M.; McKinney, A.; Fava, M. (2012). "Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial". Journal of Psychiatric Research. 46 (1): 64–71. doi:10.1016/j.jpsychires.2011.09.003. PMID 21925682. 

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