Eplivanserin (SR-46,349; planned trade name Ciltyri) was an experimental drug for the treatment of

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

which was being developed by

Sanofi Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

. 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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

and the European Medicines Agency.

Mechanism of action

Eplivanserin is an inverse agonist on the serotonin receptor subtype 5-HT_2A. In contrast to older sedating drugs acting on 5-HT_2A receptors (e.g.,

mirtazapine Mirtazapine, sold under the brand name Remeron amongst others, is an Atypical antidepressant, atypical antidepressant, and as such is used primarily to treat Depression (mood), depression. Its effects may take up to four weeks, but can also man ...

clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...

risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection (subcutaneous or intramuscular). The injectable versions ...

), eplivanserin has practically no affinity to dopamine,

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered ...

and adrenergic receptors.

Study results

In a placebo controlled

Phase II clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

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 are reacted together to give dimethylaminoacetoxime (DMA acetoxime)
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(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