Summary
Intraperitoneal administration of pargyline HCl induced a dose-dependent accumulation of 3-methoxytyramine and normetanephrine in mouse brainin vivo. As judged by the decrease of 5-hydroxyindole acetic acid levels a dose of 200 mg/kg of pargyline appeared to inhibit monoamine oxidase completely. This dose led to an approximately linear accumulation of 3-methoxytyramine and normetanephrine during the first 3 hours.γ-Butyrolactone, 750 mg/kg i.p. reduced the accumulation of 3-methoxytyramine despite a marked increase of dopamine. (+)-Amphetamine stimulated 3-methoxytyramine as well as normetanephrine accumulation at doses of 3 and 10 mg/kg i.p.
In line with the concept of receptor-mediated negative feedback control of catecholaminergic transmission the dopamine receptor agonists apomorphine, 0.3 mg/kg i.p., lisuride, 0.05–0.3 mg/kg i.p., and bromocriptine, 10 mg/kg i.p., decrease 3-methoxytyramine formation while the dopamine receptor blocking agent haloperidol, 1 mg/kg i.p., led to a 3-fold increase. Theα-adrenoceptor agonist clonidine, 0.1 mg/kg i.p., reduced the formation of normetanephrine and theα-adrenoceptor antagonists yohimbine, 10 mg per kg i.p., phenoxybenzamine, 20 mg/kg i.p., and mianserine, 50 mg/kg i.p., stimulated normetanephrine accumulation 1.5- to 4-fold.
3-Methoxytyramine and normetanephrine accumulating after inhibition of monoamine oxidase appear to be reliable indicators of dopamine and noradrenaline release and metabolism.
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Agid, Y., Javoy, F., Youdim, M. B. H. Monoamine oxidase and aldehyde dehydrogenase activity in the striatum of rats after 6-hydroxydopamine lesion of the nigrostriatal pathway. Brit. J. Pharmacoi.48, 175–178 (1973).
Andén, N.-E., Roos, B.-E., Werdinius, B. Effects of chlorpromazine haloperidol and reserpine on the levels of phenolic acids in rabbit corpus striatum. Life Sci.3, 149–158 (1964).
Andén, N.-E., Grabowska, M., Strömbom, U. Different alpha-adreno-receptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn-Schmiedeberg's Arch. Pharmacol.292, 43–52 (1976).
Atack, C. V. The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay. Brit. J. Pharmacol.48, 669–714 (1973).
Atack, C. V., Lindqvist, M. Conjoint native and orthophthaldialdehyde-condensate assays for the fluorimetric determination of 5-hydroxy-indoles in brain. Naunyn-Schmiedeberg's Arch. Pharmacol.279, 267 to 284 (1973).
Atack, C. V., Magnusson, T. A procedure for the isolation of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from the same tissue sample using a single column of strongly acidic cation exchange resin. Acta pharmacol. toxicol.42, 35–57 (1978).
Baumann, P. A., Maitre, L. Blockade of presynapticα-receptors and of amine uptake in the rat brain by the antidepressant mianserine. Naunyn-Schmiedeberg's Arch. Pharmacol.300, 31–37 (1977).
Carlsson, A., Lindqvist, M., Magnusson, T. On the biochemistry and possible functions of dopamine and noradrenaline in brain. In: Ciba Foundation Symposium on Adrenergic Mechanisms (Wolstenholme, G. E., O'Connor, M., eds.), pp. 432–439. London: J. & A. Churchill Ltd. 1960.
Carlsson, A., Hillarp, N. E. Formation of phenolic acids in brain after administration of 3, 4-dihydroxyphenylalanine. Acta physiol. scand.55, 95–100 (1962).
Carlsson, A., Lindqvist, M. Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta pharmacol. toxicol.20, 140–144 (1963).
Costa, E., Neff., N. H. Isotopic and non-isotopic measurements of the rate of catecholamine biosynthesis. In: Biochemistry and Pharmacology of the Basal Ganglia (Costa, E., Cote, L. J., Yahr, M. D., eds.), pp. 141 to 158. New York: Raven Press. 1966.
Bertler, A., Carlsson, A., Rosengren, E. A method for the fluorimetric determination of adrenaline and noradrenaline in tissues. Acta physiol. scand.44, 273–292 (1958).
Di Giulio, A. M., Groppetti, A., Cattabeni, F., Galli, C. L., Maggi, A., Algeri, S., Ponzio, F. Significance of dopamine metabolites in the evaluation of drugs acting on dopaminergic neurons. Eur. J. Pharmacol.52, 201–207 (1978).
Galli, C. L., Cattabeni, F., Eros, T., Spano, P. F., Algeri, S., Di Giulio, A., Groppetti, A. A mass fragmentographic assay of 3-methoxytyramine in rat brain. J. Neurochem.27, 795–798 (1976).
Glowinski, J., Cheramy, A., Giorguieff, M. F. In vivo and in vitro release of dopamine. In: The Neurobiology of Dopamine (Horn, A. S., Korf, J., Westerink, B. H. C., eds.), pp. 199–216. New York: Academic Press. 1979.
Groppetti, A., Parenti, M., Galli, C. L., Bugatti, A., Cattabeni, F., Di Giulio, A. M., Racagni, G. 3-Methoxytyramine and different neuroleptics: dissociation from HVA and DOPAC. Life Sci.23, 1763–1768 (1978).
Guldberg, H. C., Sharman, D. F., Tegerdine, P. R. Some observations on the estimation of 3-methoxytyramine in brain tissue. Brit. J. Pharmacol.42, 505–511 (1971).
Javoy, F., Youdim, M. B. H., Agid, Y., Glowinski, J. Early effects of monoamine oxidase inhibitors on dopamine metabolism and monoamine oxidase activity in the neostriatum of the rat. J. Neural Transm.34, 279–289 (1973).
Jonason, J., Rutledge, C. O. The effect of protriptyline on the metabolism of dopamine and noradrenaline in rabbit brain in vitro. Acta physiol. scand.73, 161–175 (1968).
Kehr, W. A method for the isolation and determination of 3-methoxytyramine in brain tissue. Naunyn-Schmiedeberg's Arch. Pharmacol.284, 149–158 (1974).
Kehr, W. 3-Methoxytyramine as an indicator of impulse-induced dopamine release in rat brain in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol.293, 209–215 (1976).
Kehr, W., Lindqvist, M., Carlsson, A. Distribution of dopamine in the rat cerebral cortex. J. Neural Transm.38, 173–180 (1976).
Kehr, W. Effect of lisuride and other ergot derivatives on monoaminergic mechanisms in rat brain. Eur. J. Pharmacol.41, 261–273 (1977).
Kehr, W., Speckenbach, W., Zimmermann, R. Interaction of haloperidol andγ-butyrolactone with (+)-amphetamine-induced changes in monoamine synthesis and metabolism in rat brain. J. Neural Transm.40, 129–147 (1977).
Korf, J., Grasdijk, L., Westerink, B. H. C. Effects of electrical stimulation of the nigrostriatal pathway of the rat on dopamine metabolism. J. Neurochem.26, 579–584 (1976).
Leonard, B. E. Some effects of a new tetracyclic anti-depressant compound, Org GB 94 on the metabolism of monoamines in the rat brain. Psychopharmacologia (Berl.)36, 221–236 (1974).
Liljequist, S., Carlsson, A. Alteration of central catecholamine metabolism following acute administration of ethanol. J. Pharm. Pharmacol.30, 730–738 (1978).
Lindqvist, M. Quantitative estimation of 5-hydroxy-3-indole acetic acid and 5-hydroxytryptophan in the brain following isolation by means of a strong cation exchange column. Acta pharmacol. toxicol.29, 303–313 (1971).
McLean, J. R., McCartney, M. Effect of d-amphetamine on rat brain noradrenaline and serotonin. Proc. Soc. Exp. Biol. Med.107, 77–79 (1961).
Moore, K. E., Lariviere, E. W. Effects of d-amphetamine and restraint on the content of norepinephrine and dopamine in rat brain. Biochem. Pharmacol.12, 1283–1288 (1963).
Roth, R. H., Walters, J. R., Aghajanian, G. K. Effect of impulse flow on the release and synthesis of DA in the rat striatum. In: Frontiers in Catecholamine Research (Snyder, S. H., Usdin, E., eds.), pp. 567–574. New York: Pergamon Press. 1973.
Scheel-Krüger, J. Studies on the accumulation of O-methylated dopamine and noradrenaline in the rat brain following various neuroleptics, thymoleptics and aceperone. Arch. int. Pharmacodyn.195, 372–378 (1972 a).
Scheel-Krüger, J. Behavioural and biochemical comparison of amphetamine derivatives, cocaine, benztropine and tricyclic anti-depressant drugs. Eur. J. Pharmacol.18, 63–73 (1972 b).
Starke, K. Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Biochem. Pharmacol.77, 1–124 (1977).
Waldmeier, P. C., Lauber, J., Blum, W., Richter, W. J. The significance of 3-methoxytyramine (MT) as an indicator of dopamine (DA) release. Naunyn-Schmiedeberg's Arch. Pharmacol. Suppl.311, R 58 (1980).
Westerink, B. H. C. Further studies on the sequence of dopamine metabolism in the rat brain. Eur. J. Pharmacol.56, 313–322 (1979 a).
Westerink, B. H. C. Effects of drugs on the formation of 3-methoxytyramine, a dopamine metabolite in the substantia nigra, striatum, nucleus accumbens and tuberculum olfactorium of the rat. J. Pharm. Pharmacol.31, 94–99 (1979 b).
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Kehr, W. 3-methoxytyramine and normetanephrine as indicators of dopamine and noradrenaline release in mouse brainin vivo . J. Neural Transmission 50, 165–178 (1981). https://doi.org/10.1007/BF01249138
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DOI: https://doi.org/10.1007/BF01249138