Determination of 3‐Methoxytyramine in Rat Brain by HPLC with Electrochemical Detection and Its Correlation with Dopamine Function After Administration of a Monoamine Oxidase Inhibitor and L‐3,4‐Dihydroxyphenylalanine

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Abstract
3-Methoxytyramine (3-MT), normally a minor metabolite of 3,4-dihydroxyphenylethylamine (dopamine) in brain, becomes the sole product of metabolism following the administration of a monoamine oxidase (MAO) inhibitor. A simplified reverse-phase HPLC method for 3-MT employing electrochemical detection is fully described. This method has a detection limit of 0.1 μg/g brain wet weight and is sensitive enough to detect 3-MT in individual brain regions after rats have been pretreated with an MAO inhibitor. Administration of tranylcypromine (TCP, 10 mg/kg) and L-3,4-dihydroxyphenylalanine (L-DOPA) (10-50 mg/kg) produced a dose-dependent linear increase in 3-MT concentrations in the dopaminergjc brain regions n. cauda-tus (r = 0.95; p < 0.01) and n. accumbens (r = 0.96; p <0.01). This treatment also produced a dose-dependent increase in behavioural activity in rats (r = 0.88; p <0.01). Furthermore, a good correlation was found between the activity responses of individual rats and the accumulation of 3-MT after TCP/L-DOPA in both n. caudatus (r = 0.76; p <0.01) and n. accumbens (r = 0.84; p <0.01). These data describe a simple and sensitive HPLC analysis technique for 3-MT and demonstrate that following administration of an MAO inhibitor this metabolite may provide a useful monitor of central dopamine function.

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