Amitifadine

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Amitifadine
Systematic (IUPAC) name
(1R,5S)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane
Clinical data
Legal status ?
Identifiers
CAS number 410074-73-6
ATC code None
PubChem CID 11658655
ChemSpider 9833390 YesY
KEGG D10088 YesY
ChEMBL CHEMBL592374 YesY
Chemical data
Formula C11H11Cl2N 
Mol. mass 228.118 g/mol
 YesY (what is this?)  (verify)

Amitifadine (am-i-TIF-a-deen), also known as DOV-21,947 or EB-1010, is an antidepressant drug being developed by Euthymics Bioscience Inc.[1] It is a so-called triple reuptake inhibitor (TRI) or serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI).[1]

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.[1] The IC50 values for serotonin, norepinephrine and dopamine uptake are 12, 23 and 96 nM, respectively

Compound Uptake Binding
5-HT NE DA SERT NET DAT
216,303 14 20 78 190 380 190
21,947 12 23 96 100 260 210
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.[2] Results in a small clinical trial indicated that amitifadine had statistically significant antidepressant effects and was well tolerated.[3]

References

  1. ↑ 1.0 1.1 1.2 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. 
  2. ↑ 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. 
  3. ↑ 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. 
Anxiolytics (N05B)
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α2δ VDCC Blockers
5-HT1A Agonists
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M: PSO/PSI

mepr

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)


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