befiradol befiradol befiradol (f-13,640; nlx-112) is an experimental drug being studied for the treatment of levodopa-induced dyskinesia. it is a potent and selective 5-ht1a receptor full agonist. befiradolclinical dataatc codenonelegal statuslegal status in general: uncontrolled identifiers iupac name 3-chloro-4-fluorophenyl-methyl)piperidin-1-yl]methanone cas number208110-64-9 npubchem cid9865384iuphar/bps3925chemspider8041076 yuniirat9oha1yhchemblchembl45305 ycomptox dashboard (epa)dtxsid90943058 chemical and physical dataformulac20h22clf2n3omolar mass393.86 g·mol−13d model (jsmol)interactive image smiles cc1ccc(nc1)cncc2(ccn(cc2)c(=o)c3ccc(c(c3)cl)f)f inchi inchi=1s/c20h22clf2n3o/c1-14-2-4-16(25-11-14)12-24-13-20(23)6-8-26(9-7-20)19(27)15-3-5-18(22)17(21)10-15/h2-5,10-11,24h,6-9,12-13h2,1h3 ykey:pkzxlmvxbzictf-uhfffaoysa-n y ny (what is this?) (verify) pharmacology in recombinant cell lines expressing human 5-ht1a receptors, befiradol exhibits high agonist efficacy for a variety of signal transduction read-outs, including erk phosphorylation, g-protein activation, receptor internalization and adenylyl cyclase inhibition. in rat hippocampal membranes it preferentially activates galphao proteins. in neurochemical experiments, befiradol activated 5-ht1a autoreceptors in rat dorsal raphe nucleus as well as 5-ht1a heteroreceptors on pyramidal neurons in the frontal cortex. it has powerful analgesic and antiallodynic effects comparable to those of high doses of opioid painkillers, but with fewer and less prominent side effects, as well as little or no development of tolerance with repeated use. a structure–activity relationship (sar) study revealed that replacement of the dihalophenyl moiety by 3-benzothienyl increases maximal efficacy from 84% to 124% (ki=2.7 nm). history befiradol was discovered and developed by pierre fabre médicament, a french pharmaceuticals company. in september 2013, befiradol was out-licensed to neurolixis, a california-based biotechnology company. neurolixis announced that it intends to re-purpose befiradol for the treatment of levodopa-induced dyskinesia in parkinson's disease. in support of this indication, neurolixis received several research grants from the michael j. fox foundation and preclinical data was published describing the activity of befiradol in animal models of parkinson's disease. in january 2018, the british charity parkinson's uk announced that it had awarded neurolixis a grant to advance development of befiradol up to clinical phase in parkinson's disease patients. clinical ph2a trial for dyskinesia in parkinson's disease in march 2019, neurolixis announced that the us food and drug administration (fda) gave a positive response to neurolixis' investigational new drug (ind) application for nlx-112 to be tested in a phase 2 clinical study in parkinson's disease patients with troublesome levodopa-induced dyskinesia. studies published in 2020 using non-human primate models of parkinson's disease, (mptp-treated marmosets and mptp-treated macaques), found that befiradol potently reduced levodopa-induced dyskinesia at oral doses as low as 0.1 to 0.4 mg/kg. on 22 november 2020, the sunday times reported that the two charities, parkinson's uk and michael j. fox foundation, were jointly investing $2 million to support a clinical trial on befiradol in parkinson's disease patients with troublesome levodopa-induced dyskinesia, a potentially "life changing" drug. on 23 november 2020, parkinson's uk and michael j. fox foundation, confirmed their funding in an official announcement. neurolixis announced on 30 november 2021 the start of patient recruitment in the clinical trial. the trial is listed on the u.s. national library of medicine clinical trials register. on 20 march 2023, a joint press release from neurolixis, parkinson's uk and michael j. fox foundation announced that the clinical trial had met its primary endpoint of safety and tolerability, and also the secondary endpoint of efficacy in reducing levodopa-induced dyskinesia in the patients. 18f-befiradol as an agonist pet radiotracer for brain imaging as well as studies on befiradol for treatment of movement disorders, other researchers have investigated it as a novel radiotracer for brain imaging studies by positron emission tomography. thus befiradol labeled with (also known as 18f-f13640) has been used to study the distribution of serotonin 5-ht1a receptors in rat, cat, macaque and human. because befiradol is an agonist, it enables the detection of 5-ht1a receptors which are specifically in a functionally active state, whereas antagonist radiotracers label the total receptor population.