Mefway is a serotonin 5-HT_1A

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...

used in medical research, usually in the form of mefway ( ¹⁸F) as a

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...

(PET) radiotracer.

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 formula – that is, the same number of atoms of each element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the existence or possibili ...

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: Sociology * Trans, a sociological term which may refer to: ** Transgender, people who identify themselves with a gender that di ...

'' 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 Neurodegeneration, neurodegenerative disorder, characterized by the loss of dopaminergic neurons in th ...

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 The raphe nuclei (, "seam") are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as autoreceptors in the brain and decrease the r ...

. 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 2-Methoxyphenyl compounds Carboxamides 2-Pyridyl compounds PET radiotracers