Eplivanserin (SR-46,349; planned trade name Ciltyri) was an experimental drug for the treatment of insomnia which was being developed by Sanofi Aventis. Sanofi Aventis announced in December 2009 that it was withdrawing its application for approval of eplivanserin from both the U.S. Food and Drug Administration and the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

Mechanism of action

Eplivanserin is an

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

on the

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...

subtype 5-HT_2A. In contrast to older

sedating Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

drugs acting on 5-HT_2A receptors (e.g., mirtazapine, clozapine, risperidone), eplivanserin has practically no affinity to

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

, histamine and

adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...

Study results

In a placebo controlled Phase II clinical trial with 351 subjects, eplivanserin reduced the sleep latency by 39 minutes (versus 26 minutes under placebo).

Synthesis

] The condensation between 2'-Fluoroacetophenone 45-27-2(5) & 4-hydroxybenzaldehyde 23-08-0(6) give a chalcone intermediate (also an enone), i.e
CID:53982926
(7). (2-chloroethyl)dimethylamine (CDMA) &

acetone oxime Acetone oxime (acetoxime) is the organic compound with the formula (CH3)2CNOH. It is the simplest example of a ketoxime. It is a white crystalline solid that is soluble in water, ethanol, ether, chloroform, and ligroin. It is used as a reagent ...

are reacted together to give dimethylaminoacetoxime (DMA acetoxime)
CID:16641114
(3). Convergent synthesis gives the product as a mixture of isomers.

References

Hypnotics Phenols Fluoroarenes Ketoximes Dimethylamino compounds {{sedative-stub

Mechanism of action

Study results

Synthesis

See also

References