Mefway (18F)

Mefway (¹⁸F)

Systematic (IUPAC) name
4-[(18F)fluoromethyl]-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexane-1-carboxamide
Clinical data
Pregnancy category	N/A
Legal status	Research compound
Identifiers
CAS Number	943962-60-5
ATC code	none
PubChem	CID: 11963740
ChemSpider	10137857
Chemical data
Formula	C26H35FN4O2
Molecular mass	453.583 g/mol
SMILES COC1=CC=CC=C1N2CCN(CC2)CCN(C3=CC=CC=N3)C(=O)C4CCC(CC4)C[18F]
InChI InChI=1S/C26H35FN4O2/c1-33-24-7-3-2-6-23(24)30-17-14-29(15-18-30)16-19-31(25-8-4-5-13-28-25)26(32)22-11-9-21(20-27)10-12-22/h2-8,13,21-22H,9-12,14-20H2,1H3/i27-1 Key:BQGLPDFQLBNUGU-FMLNDMEQSA-N

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.

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 with regard to the cyclohexane ring, of which the trans conformation has the higher 5-HT_1A specificity.

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 phenomena was effectively suppressed by cytochrome P450 inhibitor (i.e. fluconazole). Animal models of Parkinson's disease 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.