Summary
The kinetics and tissue distribution of amphetamine and its metabolites p-hydroxyamphetamine (p-OH-A) and p-hydroxynorephedrine (p-OH-NE) were investigated in young adult (3–4 months) and old (20–25 months) male rats, after i.p. injection of 5 mg/kg tritium labelled d-amphetamine. The concentrations of these drugs were determined in plasma, cerebral cortex, brainstem and hypothalamus, by thin layer chromatography.
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1.
From 60 min up to 4 hrs after injection of amphetamine the concentration of a mphetamine in plasma and brain tissue of old rats was significantly (P<0.05 higher than in young adult animals. In both age groups the levels of amphetamine in cerebral cortex > brain stem > hypothalamus.
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2.
The blood-brain barrier is permutle to p-OH-A; 10 to 20 min after i.v. injection of 10 μCi/kg of p-OH-A (10 mCi/m mole) the ratio brain/blood plasma was found to be 1:3. The half life of p-OH-A in blood plasma was almost identical after injection of amphetamine and p-OH-A (90 min and 98 min respectively).
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3.
The levels of p-OH-NE in different brain areas were significantly lower (P<0.05) in old animals than in young adult rats 4 hrs after application of amphetamine. This metabolite of amphetamine shows a higher concentration in the hypothalamus earlier than in other brain regions.
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References
Axelrod, J.: Studies on sympathomimetic amines. II. The biotransformation and physiological disposition of d-amphetamine, d−p-hydroxyamphetamine and d-methyl-amphetamine. J. Pharmacol. exp. Ther. 110, 315–326 (1954)
Axelrod, J.: Amphetamine metabolism, physiological disposition and its effects on catecholamine storage. In: E. Costa, S. Garattini (Eds.): International Symposium on Amphetamines and Related Compounds. Proc. of the Mario Negri Inst. for Pharmacol. Res., Milan/Italy, pp. 207–216. New York: Raven Press and Amsterdam: North Holland Publ. Comp. 1970
Beckett, A. H.: Kinetics of the absorption and elimination of “amphetamines” in normal humans. In: F. Sjöqvist and M. Tottie (Eds.): Abuse of central stimulants, pp. 375–408. Stockholm: Almqvist & Wiksell, 1969
Brodie, B. B., Cho, A. K., Gessa, G. L.: Possible role of p-hydroxynorepinephrine in the depletion of norepinephrine induced by d-amphetamine and in tolerance to this drug. In: E. Costa and S. Garattini (Eds.): International Symposium on Amphetamines and Related Compounds. Proc. of the Mario Negri Inst. for Pharmacol. Res., Milan/Italy, pp. 217–230. New York: Raven Press and Amsterdam: North Holland Publ. Comp. 1970
Costa, E., Gropetti, A.: Biosynthesis and storage of catecholamines in tissue of rats injected with various doses of d-amphetamine. In: E. Costa and S. Garattini (Eds.): International Symposium on Amphetamines and Related Compounds. Proc. of the Mario Negri Inst. for Pharmacol. Res., Milan/Italy, pp. 231–255. New York: Raven Press, and Amsterdam: North Holland Publ. Comp. 1970
Davis, J. M., Kopin, J. J., Lemberger, L., Axelrod, J.: Effects of urinary pH on amphetamine metabolism. Ann. N. Y. Acad. Sci. 179, 493–501 (1971)
Garattini, S.: Effects of amphetamine and fenfluramine in different experimental conditions. In: F. Sjöqvist and M. Tottie (Eds.): Abuse of Central Stimulants pp. 323–337. Stockholm: Almqvist & Wiskell 1969
Glowinski, J., Axelrod, J.: Effect of drugs on the uptake release and metabolism of 3H-norepinephrine in the rat brain. J. Pharmacol. exp. Ther. 149, 43 (1965)
Goldstein, M., Anagnoste, B.: The conversion in vivo of d-amphetamine to (+)-p-hydroxynorephedrine. Biochim. biophys. Acta (Amst.) 107, 166 (1965)
Kopin, I. J., Fischer, J. E., Musacchir, J. M., Horst, W. D., Weise, V. K.: False neurochemical transmitters and the mechanism of sympathetic blockade by monoamineoxidase inhibitors. J. Pharmacol. exp. Ther. 147, 186 (1965)
Lewander, T.: Displacement of brain and heart noradrenaline by p-hydroxynorephedrine after administration of p-hydroxyamphetamine. Acta pharmacol. (Kbh.) 29, 20–32 (1971)
Maickel, R. P., Cox, R. H., Jr., Miller, F. P., Segal, D. S., Russel, R. W.: Correlation of brain levels of drugs with behavioral effects. J. Pharmacol. exp. Ther. 165, 216–224 (1969)
Placidi, G. F., Masuoka, D. T., Earle, R. W.: Distribution of (14C)-amphetamine in mouse brain; an autoradiographic study. Brain Res. 38, 339–405 (1972)
Reis, D. J., Molinoff, P. P.: Brain dopamine-β-hydroxylase: Regional distribution and effects of lesions and 6-hydroxydopamine on activity. J. Neurochem. 19, 195–204 (1972)
Ritschel, W. A.: Angewandte Biopharmazie, p. 108. Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH., 1973
Rommelspacher, H., Coper, H., Lison, H., Fähndrich, Ch., Strauss, S.: Über den Einfluß von Rezeptorenblockern und zentral wirkenden Substanzen auf die Thermoregulation und den Katecholaminhaushalt bei erwachsenen und alten Ratten. act. gerontologie 1, 5–8 (1972)
Sjoerdsma, A., Studnitz, W. von: Dopamine-β-oxidase activity in man, using hydroxyamphetamine as substrate. Brit. J. Pharmacol. 20, 278 (1963)
Stahl, E.: Dünnschichtchromatographie, 2. Aufl., p. 979. Berlin-Heidelberg-New York: Springer 1967
Young, R. L., Gordon, M. W.: The disposition of (14C)-amphetamine in rat brain. J. Neurochem. 9, 161–167 (1962)
Ziem, M., Coper, H., Broermann, I., Strauss, S.: Vergleichende Untersuchungen über einige Wirkungen des Amphetamins bei Ratten verschiedenen Alters. Naunyn-Schmiedeberg's Arch. Pharmak. 257, 208–223 (1970)
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Honecker, H., Coper, H. Kinetics and metabolism of amphetamine in the brain of rats of different ages. Naunyn-Schmiedeberg's Arch. Pharmacol. 291, 111–121 (1975). https://doi.org/10.1007/BF00500043
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DOI: https://doi.org/10.1007/BF00500043