Summary
The value of 3-methoxytyramine (3-MT) as an indicator of impulse-related dopamine (DA) release has been assessed in rat corpus striatum. Moreover, the turnover of 3-MT was estimated by measuring its disappearance rate after COMT inhibition. Quantitation of 3-MT and DA was performed by gas chromatography/mass spectrometry (selected ion monitoring).
Haloperidol in doses between 0.05 and 3 mg/kg p.o. did not increase endogenous 3-MT levels at any time up to 24 h after its administration, whereas it dose-dependently increased homovanillic acid and 3,4-dihydroxyphenylacetic acid. However, in doses above 0.1 mg/kg p.o., it enhanced the accumulation of 3-MT in clorgyline-pretreated animals. Conversely, baclofen in doses of 2 mg/kg i.p. and above decreased endogeneous 3-MT levels, but reduced the accumulation of this amine only poorly at 20 mg/kg i.p. in clorgyline-pretreated rats. A number of dopamine agonists, apomorphine (0.5 mg/kg i.v.), dipropyl-ADTN (0.03 mg/kg i.v.), but not bromocriptine (1 mg/kg i.v.) reduced endogenous 3-MT levels 10 min after administration by approximately 50%.
The DA releasing agents d-amphetamine and methylphenidate showed different effects: the former increased endogenous 3-MT greatly, whereas the latter was without effect. The difference is likely to be related to the MAO inhibitory properties of amphetamine.
3-MT disappeared rapidly after COMT inhibition with 50 mg/kg i.v. tropolone (half-life of the initial disappearance about 1 min). The curve flattened off after 5–10 min. Turnover was calculated to be about 7 nmol/g/h, which corresponds to about a third of the turnover of DA.
Our results suggest that an important part of DA metabolism occurs through 3-MT and that this amine is very effectively deaminated by MAO-A, so effectively indeed that increased formation does not increase its endogeneous levels. It appears, therefore, that 3-MT is not suitable as an indicator of increased DA release. However, it seems to have some value for an assessment of lowered DA release.
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Waldmeier, P.C., Lauber, J., Blum, W. et al. 3-methoxytyramine: Its suitability as an indicator of synaptic dopamine release. Naunyn-Schmiedeberg's Arch. Pharmacol. 315, 219–225 (1981). https://doi.org/10.1007/BF00499838
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DOI: https://doi.org/10.1007/BF00499838