Skip to main content

New Drug Approvals 2012 - Pt. XXII - Perampanel (FycompaTM)

By


ATC Code: N03AX22
Wikipedia: Perampanel

On October 22nd 2012 the FDA approved Perampanel (research code: E2007, ER-155055-90, trade name Fycompa, CHEMBL1214124). Perampanel is an orally administered drug to be used as an adjunctive therapy for the treatment of partial-onset seizures with or without secondary generalized seizures in patients with epilepsy.

Epileptic seizures are defined as "abnormal excessive or synchronous neuronal activity in the brain". The net symptoms can be very diverse, from severe thrashing movements to a very mild brief loss of awareness. Approximately 4% of the population will have experienced a unprovoked seizure by the age of 80, with a 30-50% chance of repeat in this group. Seizures can last from a few seconds to a state of life threatening persistent seizure (known as status epilepticus).

Approximately 25 % of the people suffering from a seizure or  status epilepticus will be diagnosed to have epilepsy. Treatment may reduce the chance of a second seizure by as much as 50%.

Perampanel acts by non-competitively inhibiting the ionotropic α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) glutamate receptor. This receptor consists of a heteromeric combination of 2 out of 4 known subunits GluR-1 - GluR4 (respectively: CHEMBL2009, CHEMBL4016, CHEMBL3595 and CHEMBL3190 or Uniprot 42261, 42262, 42263 and 48058). Of these, the combinations GluR-1/GluR-2 and GluR-2/GluR-3 are the most frequent. The specific mechanism by which Perampanel exerts its antiepileptic effect in humans has not been fully elucidated.



Fycompa is a small molecule drug with a molecular mass of 349.4 g/mol, an AlogP of 3.57 , 3 rotatable bonds and does not violate the rule of 5. Canonical SMILES : O=C1N(C=C(C=C1c2ccccc2C#N)c3ccccn3)c4ccccc4
InChi: InChI=1S/C23H15N3O/c24-15-17-8-4-5-11-20(17)21-14-18(22-12-6-7-13-25-22)16-26(23(21)27)19-9-2-1-3-10-19/h1-14,16H

The recommended starting dose of Perampanel in the absence of other CYP3A4 enzyme-inducing antiepileptic drugs is 2 mg once daily taken orally at bedtime (and can be incremented to the recommended dose range of 8 mg to 12 mg once daily). The recommended starting dose of Perampanel in the presence of CYP3A4 enzyme-inducing antiepileptic drugs is 4 mg and patients should be monitored closely for response.

Perampanel is extensively metabolized via initial oxidation and sequential glucuronidation. Oxidative metabolism is mediated by CYP3A4 and/or CYP3A5 based on results of in vitro studies using recombinant human CYPs and human liver microsomes. Other CYP enzymes may also be involved.

The license holder is Eisai Inc. and the full prescribing information can be found here.
Labels:

Comments

Post a Comment

Popular posts from this blog

SureChEMBL Available Now

By
Followers of the ChEMBL group's activities and this blog will be aware of our involvement in the migration of the previously commercially available SureChem chemistry patent system, to a new, free-for-all system, known as SureChEMBL. Today we are very pleased to announce that the migration process is complete and the SureChEMBL website is now online. SureChEMBL provides the research community with the ability to search the patent literature using Lucene-based keyword queries and, much more importantly, chemistry-based queries. If you are not familiar with SureChEMBL, we recommend you review the content of these earlier blogposts here and here . SureChEMBL is a live system, which is continuously extracting chemical entities from the patent literature. The time it takes for a new chemical in the patent literature to become searchable in the SureChEMBL system is 1-2 days (WO patents can sometimes take a bit longer due to an additional reprocessing step). At time of writi
4 comments
Read more

New SureChEMBL announcement

By
(Generated with DALL-E 3 ∙ 30 October 2023 at 1:48 pm) We have some very exciting news to report: the new SureChEMBL is now available! Hooray! What is SureChEMBL, you may ask. Good question! In our portfolio of chemical biology services, alongside our established database of bioactivity data for drug-like molecules ChEMBL , our dictionary of annotated small molecule entities ChEBI , and our compound cross-referencing system UniChem , we also deliver a database of annotated patents! Almost 10 years ago , EMBL-EBI acquired the SureChem system of chemically annotated patents and made this freely accessible in the public domain as SureChEMBL. Since then, our team has continued to maintain and deliver SureChEMBL. However, this has become increasingly challenging due to the complexities of the underlying codebase. We were awarded a Wellcome Trust grant in 2021 to completely overhaul SureChEMBL, with a new UI, backend infrastructure, and new f
Post a Comment
Read more

ChEMBL & SureChEMBL anniversary symposium

By
  In 2024 we celebrate the 15th anniversary of the first public release of the ChEMBL database as well as the 10th anniversary of SureChEMBL. To recognise this important landmark we are organising a two-day symposium to celebrate the work achieved by ChEMBL and SureChEMBL, and look forward to its future.   Save the date for the ChEMBL 15 Year Symposium October 1-2, 2024     Day one will consist of four workshops, a basic ChEMBL drug design workshop; an advanced ChEMBL workshop (EUbOPEN community workshop); a ChEMBL data deposition workshop; and a SureChEMBL workshop. Day two will consist of a series of talks from invited speakers, a few poster flash talks, a local nature walk, as well as celebratory cake. During the breaks, the poster session will be a great opportunity to catch up with other users and collaborators of the ChEMBL resources and chat to colleagues, co-workers and others to find out more about how the database is being used. Lunch and refreshments will be pro
Post a Comment
Read more

ChEMBL 34 is out!

By
We are delighted to announce the release of ChEMBL 34, which includes a full update to drug and clinical candidate drug data. This version of the database, prepared on 28/03/2024 contains:         2,431,025 compounds (of which 2,409,270 have mol files)         3,106,257 compound records (non-unique compounds)         20,772,701 activities         1,644,390 assays         15,598 targets         89,892 documents Data can be downloaded from the ChEMBL FTP site:  https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/ Please see ChEMBL_34 release notes for full details of all changes in this release:  https://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/releases/chembl_34/chembl_34_release_notes.txt New Data Sources European Medicines Agency (src_id = 66): European Medicines Agency's data correspond to EMA drugs prior to 20 January 2023 (excluding vaccines). 71 out of the 882 newly added EMA drugs are only authorised by EMA, rather than from other regulatory bodies e.g.
Post a Comment
Read more

RDKit, C++ and Jupyter Notebook

By Eloy
Fancy playing with RDKit C++ API without needing to set up a C++ project and compile it? But wait... isn't C++ a compiled programming language? How this can be even possible? Thanks to Cling (CERN's C++ interpreter) and xeus-cling jupyter kernel is possible to use C++ as an intepreted language inside a jupyter notebook! We prepared a simple notebook showing few examples of RDKit functionalities and a docker image in case you want to run it. With the single requirement of docker being installed in your computer you'll be able to easily run the examples following the three steps below: docker pull eloyfelix/rdkit_jupyter_cling docker run -d -p 9999:9999 eloyfelix/rdkit_jupyter_cling open  http://localhost:9999/notebooks/rdkit_cling.ipynb  in a browser
Post a Comment
Read more