Safinamide

Safinamide

Safinamide
Systematic (IUPAC) name
N2-{4-[(3-fluorobenzyl)oxy]benzyl}-L-alaninamide
Clinical data
Legal status
  • Investigational
Identifiers
CAS number  N
202825-46-5 (mesylate)
ATC code None
PubChem
ChemSpider  YesY
UNII  YesY
KEGG  N
ChEMBL  YesY
Synonyms (2S)-2-[[4-[(3-Fluorophenyl)methoxy]phenyl] methylamino]propanamide
Chemical data
Formula C17H19FN2O2 
Mol. mass 302.34 g/mol
 N   

Safinamide (EMD 1195686) is a candidate drug against Parkinson's disease with multiple methods of action.[1] In 2007, a Phase III clinical trial was started. It was scheduled to run until 2011.[2] The compound was originally discovered at Farmitalia-Carlo Erba [3] and developed by Newron Pharmaceuticals, which sold the rights to Merck-Serono in 2006. In October 2011 Merck-Serono announced that they would give all rights to develop the compound back to Newron.[4]

Potential additional uses might be restless legs syndrome (RLS) and epilepsy.[5] They were being tested in Phase II trials in 2008, but no results are available.

Adverse effects

Common adverse events in clinical trials were nausea, dizziness, tiredness, headache and backache. There was no significant difference in the occurrence of these effects between safinamide and placebo treated patients.[6]

Methods of action

Parkinson and RLS relevant mechanisms

Safinamide is a reversible and selective monoamine oxidase B inhibitor, reducing degradation of dopamine, and a glutamate release inhibitor.[6][7] It also seems to inhibit dopamine reuptake.[8] Additionally, safinamide blocks sodium and calcium channels.[7][9]

References

  1. ^ Fariello, RG (2007). "Safinamide". Neurotherapeutics 4 (1): 110–116.  
  2. ^ Study of Safinamide in Early Parkinson's Disease as Add-on to Dopamine Agonist (MOTION)
  3. ^ Pevarello, P; Bonsignori, A; Dostert, P; Heidempergher, F; Pinciroli, V; Colombo, M; McArthur, RA; Varasi, M (1998). "Synthesis and Anticonvulsant Activity of a New Class of 2-[(Arylalkyl)amino]alkanamide Derivatives". Journal of Medicinal Chemistry 41 (4): 579–590. 
  4. ^ Merck Returns Rights for Safinamide to Newron, 21 October 2011.
  5. ^ Chazot, PL (2007). "Drug evaluation: Safinamide for the treatment of Parkinson's disease, epilepsy and restless legs syndrome". Current Opinion in Investigational Drugs 8 (7): 570–579.  
  6. ^ a b H. Spreitzer (14 April 2014). "Neue Wirkstoffe – Safinamid". Österreichische Apothekerzeitung (in German) (8/2014): 30. 
  7. ^ a b Caccia, C; Maj, R; Calabresi, M; Maestroni, S; Faravelli, L; Curatolo, L; Salvati, P; Fariello, RG (2006). "Safinamide: From molecular targets to a new anti-Parkinson drug". Neurology 67 (7 Suppl 2): S18–23.  
  8. ^ Merck Serono: Vielversprechende Daten zur kognitiven Wirkung von Safinamid bei Parkinson im Frühstadium. (German) 8 June 2007.
  9. ^ Pevarello, P; Bonsignori, A; Caccia, C; Amici, R; Salvati, P; Fariello, RG; McArthur, RA; Varasi, M (1999). "Sodium channel activity and sigma binding of 2-aminopropanamide anticonvulsants". Bioorganic & Medicinal Chemistry Letters 9 (17): 2521–2524.