An iodinated derivative of moclobemide as potential radioligand for brain MAO-A exploration

Article abstract of DOI:10.1016/0024-3205(96)00074-4

In vivo evaluation of MAO-A would be of great value for the diagnosis and follow-up of therapy of depression. In order to perform this exploration by SPECT, we developed an iodinated derivative of the reversible MAO-A inhibitor, moclobemide. Ro 11-9900 was synthesized and analysed by IR, NMR and HPLC. Radioiodination was carried out by nucleophilic exchange of [¹²⁵I] on the brominated precursor, and yielded [¹²⁵I]-Ro 11-9900 with high specific activity. In vitro experiments on rat brain homogenates showed that Ro 11-9900 had poor inhibitory activity on MAO-A, as already described for moclobemide. By contrast, in vivo biodistribution in the rat brain showed that [¹²⁵I]-Ro 11-9900 accumulated in a region corresponding to the localization of-locus coeruleus known for its high density of MAO-A. Moreover, preinjection of the irreversible MAO-A inhibitor clorgyline (10 mg.kg^-1) prevented accumulation of radioactivity by 40 to 60% and we found that the radioactivity in the brain corresponded exclusively to [¹²⁵I]-Ro 11-9900 and not to a metabolite. [¹²⁵I]-Ro 11-9900 was highly accumulated in the pineal gland, both on MAO-A and on MAO-B sites. We concluded that the unmetabolized iodinated derivative of moclobemide, Ro 11-9900, preferentially labeled MAO-A in vivo in the rat brain. This compound would therefore be a potential tracer for evaluation of MAO-A by SPECT.