Mefway is a serotonin 5-HT_1A receptor antagonist used in medical research, usually in the form of mefway ( ¹⁸F) as a positron emission tomography (PET)

radiotracer A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...

Chemistry

Mefway is closely related to the research compound WAY-100,635. The compound adds a fluoromethyl group to the cyclohexyl ring of WAY-100,635 and it is effectively prepared with automation module. There are two

isomers In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. ...

with regard to the cyclohexane ring, of which the ''

trans Trans- is a Latin prefix meaning "across", "beyond", or "on the other side of". Used alone, trans may refer to: Arts, entertainment, and media * Trans (festival), a former festival in Belfast, Northern Ireland, United Kingdom * ''Trans'' (fil ...

'' conformation has the higher 5-HT_1A specificity. Mefway cis-trans comparison

Animal PET studies

In one study the uptake and retention of mefway (¹⁸F) was found to be similar to that found for ¹¹C-WAY-100,635. Head-to-head comparison of mefway (¹⁸F) and ¹¹C-WAY-100,635 have been evaluated. Since ¹¹C-WAY-100,635 is the current 'gold standard' and difficult to synthesize, a suitable fluorine-18 replacement as in mefway is highly desired. In addition, mefway (¹⁸F) showed comparable brain uptake and the target-to-reference ratios compared to fcway(¹⁸F) The ability to separately measure dissociation constant, K_D and receptor density Bmax has been shown to be of potential value rather than simply comparing binding potential, BP_ND. Multiple injection mefway PET experiments can be used for the in-vivo measurement of 5-HT_1A receptor density. Imaging studies of mefway on in vivo and ex vivo rat brains indicate that the substance binds to the known 5-HT_1A receptor regions including the dorsal raphe. These findings support that the dorsal raphe is measurable in rat PET studies. Mefway (¹⁸F) undergoes in vivo defluorination in rodent brain and this phenomenon was effectively suppressed by cytochrome P450 inhibitor (i.e. fluconazole).

Animal models of Parkinson's disease Animal models of Parkinson's disease are essential in the research field and widely used to study Parkinson's disease. Parkinson's disease is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra ...

and the acute physical stress model exhibited significant decrement of binding potential in the hippocampus

Human PET studies

First-in-human studies have shown in vivo stability of mefway (¹⁸F) and its localization to 5-HT_1A receptor-rich regions in the human brain, including the raphe nucleus. Mefway (¹⁸F) is highly selective for the human serotonin 5-HT_1A receptor and may therefore may be used to quantify serotonin 5-HT_1A receptor distribution in brain regions for the study of various central nervous system disorders.

References

{{Piperazines Radiopharmaceuticals Phenylpiperazines Phenol ethers Carboxamides 2-Pyridyl compounds PET radiotracers