Inhibition of monoamine oxidase in monoaminergic neurones in the rat brain by irreversible inhibitors.

The irreversible inhibition of monoamine oxidase (MAO) inside and outside monoaminergic neurones in the rat brain by the suicide inhibitors clorgyline, selegiline (l-deprenyl), pheniprazine, phenelzine, iproniazid, pargyline and the d- and l-enantiomers of tranylcypromine was determined. This was achieved by incubating crude synaptosomal preparations of hypothalamus and striatum from rats treated with the inhibitors 24 hr earlier, with low concentrations of [14C]serotonin (0.1 microM), [14C]-noradrenaline (0.25 microM) and [14C]dopamine (0.25 microM) in the absence and presence of selective uptake inhibitors (citalopram, maprotiline and amfonelic acid, respectively). It was found that all inhibitors inhibited the deamination of serotonin and noradrenaline outside the amine neurons at slightly lower doses than that within these neurones. This could at least in part be due to protection of MAO by the endogenous amines in these neurones. The deamination of dopamine was rather more strongly inhibited inside the neutrons than outside, particularly at higher doses. There was no indication that tranylcypromine or phenelzine was accumulated in the neurones by the membranous amine uptake mechanisms. The rate of the recovery of the deaminating activities inside and outside the serotonergic and noradrenergic neurones in hypothalamus after phenelzine and clorgyline inhibition was the same (50% recovery after 12-15 days), which indicates similar rate of synthesis of MAO in different cell types.