Safinamide

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Safinamide
Safinamide.svg
Systematic (IUPAC) name
N2-{4-[(3-fluorobenzyl)oxy]benzyl}-L-alaninamide
Clinical data
  • Investigational
Identifiers
133865-89-1 N
202825-46-5 (mesylate)
None
PubChem CID 131682
ChemSpider 116349 YesY
UNII 90ENL74SIG YesY
KEGG D10158 N
ChEMBL CHEMBL396778 YesY
Synonyms (2S)-2-[[4-[(3-Fluorophenyl)methoxy]phenyl] methylamino]propanamide
Chemical data
Formula C17H19FN2O2
302.34 g/mol
 N (what is this?)  (verify)

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[edit]

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[edit]

Parkinson and RLS relevant mechanisms[edit]

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] Safinamide has been approved by the European Medicines Agency for the treatment of adult patients with idiopathic Parkinson’s disease as add-on therapy to a stable dose of Levodopa (L-dopa) alone or in combination with other PD drugs in patients with mid-to-late-stage fluctuating disease.[10]

See also[edit]

  • Ralfinamide, Very similar structure - Different fluorine position
  • Lacosamide, used for partial-onset seizures and diabetic neuropathic pain
  • Ziconotide, a peptide analgesic

References[edit]

  1. ^ Fariello, RG (2007). "Safinamide". Neurotherapeutics 4 (1): 110–116. doi:10.1016/j.nurt.2006.11.011. PMID 17199024. 
  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. doi:10.1021/jm970599m. 
  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. PMID 17659477. 
  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. doi:10.1212/wnl.67.7_suppl_2.s18. PMID 17030736. 
  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. doi:10.1016/s0960-894x(99)00415-1. 
  10. ^ Lawrence, Janna (2015-01-19). "Safinamide recommended for approval as Parkinson’s disease therapy". The Pharmaceutical Journal (Royal Pharmaceutical Society). Retrieved 2015-01-19.