Abstract
The comparative effects of d-amphetamine, l-amphetamine, and methylphenidate were assessed in 16 normal subjects, using a double-blind, crossover placebo-controlled design. Within the dose range tested, the efficacy ratio of d-amphetamine: l-amphetamine was about 2:1, and graphic presentation of dose response scores indicated a relatively small difference in potency between the amphetamine isomers. Methylphenidate was intermediate in efficacy between d-amphetamine and l-amphetamine. The efficacy ratios for d-amphetamine: l-amphetamine on increasing euphoric mood in man were similar to the previously reported ratios of these two isomers in inducing or exacerbating psychosis in humans. These findings do not support the suggestion, made by Snyder and others, that the differential effects of d-amphetamine vs. l-amphetamine on a specific type of behavior in man could be utilized to infer the predominance of noradrenergic vs. dopaminergic mediation of amphetamine's effects on this behavior.
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References
Alles, G. A.: Comparative physiological actions of optically isomeric phenylisopropylamines. Univ. of Calif. Publ. Pharmacol. 1, 129–150 (1939)
Angrist, B., Gershon, S.: A pilot study of the pathogenic mechanism in amphetamine psychosis utilizing differential doses of d- and l-amphetamine. Pharmakopsychiatry 4, 64–75 (1971a)
Angrist, B. M., Shopsin, B., Gershon, S.: Comparative psychotomimetic effects of stereoisomers of amphetamine. Nature (Lond.) 234, 152–153 (1971b)
Arnold, L. A., Wender, P. H., McLoskey, M. M., Snyder, S. H.: Levoamphetamine and dextroamphetamine: Comparative efficacy in hyperkinetic syndrome. Arch. gen. Psychiat. 27, 816–822 (1972)
Arnold, L. E., Huestis, R. O., Smeltzer, D. J., Scheib, J., Wemmer, Colner, D.: Levoamphetamine vs. dextroamphetamine in minimal brain dysfunction. Arch. gen. Psychiat. 33, 292–301 (1976)
Arnold, L. E., Kircuk, V., Corson, S. A., Corson, E. O.: Levoamphetamine and dextroamphetamine: Differential effect on aggression and hyperkinesia in children and dogs. Amer. J. Psychiat. 130, 165–170 (1973)
Brodie, B. B., Cho, A. K., Gessa, G. L.: Possible role of p-hydroxy-norephedrine in the depletion of norepinephrine induced by d-amphetamine and in tolerance to this drug. In: Amphetamines and related compounds, E. Costa and S. Garattini, eds., pp. 219–230. New York: Raven Press 1970
Bruning, J. L., Kintz, R. L.: Computation handbook of statistics, pp. 112–115. Glenview, Ill.: Scott, Forseman 1968
Bunney, B. S., Walters, J. R., Kuhar, M. J., Roth, R. H., Aghajanian, G. K.: d- and l-amphetamine stereoisomers: Comparative potencies in affecting the firing of central dopaminergic and noradrenergic neuron. Psychopharmacol. Commun. 1, 177–190 (1975)
Caldwell, J., Dring, L. G., Williams, R. T.: Norephedrines as metabolites of (14C)amphetamine in urine in man. Biochem. J. 129, 23–24 (1972)
Chieuh, C. C., Moore, K. E.: d-Amphetamine-induced release of “newly synthesized” and “stored” dopamine from the caudate nucleus in vivo. J. Pharmacol. exp. Ther. 192, 642–653 (1975a)
Chieuh, C. C., Moore, K. E.: Blockade by reserpine of methylphenidate induced release of brain dopamine. J. Pharmacol. exp. Ther. 193, 559–563 (1975b)
Coyle, J. T., Snyder, S. H.: Catecholamine uptake by synaptosomes in homogenates of rat brains: stereospecificity in different areas. J. Pharmacol. exp. Ther. 170, 221–251 (1969)
Davis, J. M., Kopin, I. J., Lemberger, L., Axelrod, J.: Effects of urinary pH on amphetamine metabolism. Ann. N.Y. Acad. Sci. 179, 493–501 (1971)
Dring, L. G., Smith, R. L., Williams, R. T.: The metabolic fate of amphetamine in man and other species. Biochem. J. 116, 425–435 (1970)
Engen, T.: Psychophysics II scaling methods: In: Experimental psychology. J. W. Kling and L. A. Riggs, eds., pp. 47–86, New York: Holt, Rinehart and Winston 1971
Ekman, G., Frankenhauser, M., Goldberg, L., Bjerver, K., Harpe, G., Myrsten, A.: Effects of alcohol intake on subjective and objective variables over a five-hour period. Psychopharmacologia (Berl.) 4, 28–38 (1963)
Faraj, G. A., Israili, J. M., Perel, M. L., Jenkins, M. L., Holtzman, S. G., Cucinell, S. A., Dayton, P. G.: Metabolism and disposition of methylphenidate-14C:Studies in man and animals. J. Pharmacol. exp. Ther. 191, 535–547 (1974)
Ferris, R. M., Tang, F. L. M., Maxwell, R. A.: A comparison of the capacities of isomers of amphetamine, deoxypipradrol, and methylphenidate to inhibit the uptake of tritiated catecholamines into cerebral cortex slices, synaptosomal preparations of rat cerebral cortex, hypothalamus and striatum and into adrenergic nerves of rabbit aorta. J. Pharmacol. exp. Ther. 181, 407–416 (1972)
Gunne, L. M., Anggard, E.: Pharmacokinetic studies with amphetamines — relationship to neuropsychiatric disorders. J. Pharmacokinet. Biopharmaceut. 1, 481–495 (1973)
Harris, J. E., Baldessarini, R. J.: Uptake of 3H-catecholamines by homogenates of rat corpus striatum: Effects of amphetamine analogues. Neuropharmacology 12, 669–678 (1973)
Janowsky, D., Davis, J. M.: Methylphenidate, dextroamphetamine, and levoamphetamine. Arch. gen. Psychiat. 33, 304–308 (1976)
Kopin, J. J., Fischer, J. E., Musaccio, J. M., Horst, W. D., Weise, V. K.: “False neurotransmitters” and the mechanisms of sympathetic blockade by monoamine oxidase inhibitors. J. Pharmacol. exp. Ther. 147, 186 (1965)
Martin, W. R., Sloan, J. W., Sapira, J. P., Jasinski, D. R.: Physiological, subjective and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin. Pharmacol. Ther. 12, 245–257 (1971)
McNair, D. M., Lorr, M., Droppleman, L. F.: ETTS manual for profile of mood states. San Diego, Calif.: Education and Industrial Testing Service 1971
Meyerhoff, J. L., Snyder, S. H.: Catecholamines and Gilles de la Tourette's syndrome: A clinical study with amphetamine isomers. In: Advances in neurology, vol. I, A. Barbeau et al., eds. New York: Raven Press 1973
Moore, K. E., Carr, L. A., Dominic, J. A.: Functional significance of amphetamine induced release of brain catecholamines. In: Amphetamines and related compounds, E. Costa and S. Garattini, eds., pp. 371–384. New York: Raven Press 1973
Prinzmetal, M., Alles, G. A.: The central nervous stimulant effects of dextroamphetamine sulfate. Amer. J. med. Sci. 200, 665–673 (1940)
Scheel-Kruger, J.: Some aspects of the mechanism of action of various stimulant amphetamine analgues. Psychiat. Neurol. Neurochir. (Amst.) 75, 179–192 (1972)
Schildkraut, J. J.: The catecholamine hypothesis of affective disorders: a review of supporting evidence. Amer. J. Psychiat. 122, 509–522 (1965)
Smith, G., Beecher, H. K.: Amphetamine, secobarbital, and athletic performance. J. Amer. med. Ass. 172, 1502–1512 (1960)
Smith, R. C., Davis, J. M., Schlemmer, R.: Behavioral potencies of amphetamines and methylphenidate on mood and activation in man and stereotyped behavior and locomotor activity in rats. Abstract Society for Neuroscience, 4th annual meeting (1974), p. 429
Smith, R. L., Dring, L. G.: Patterns of metabolism of anorexic phenylisopropylamines in the rat. In: Amphetamines and related compounds, E. Costa and S. Garattini, eds., pp. 121–141. New York: Raven Press 1970
Snyder, S., Taylor, K. M., Coyle, J. J., Meyerhoff, J. L.: The role of brain dopamine in behavioral regulation and actions of psychotropic drugs. Amer. J. Psychiat. 127, 199–207 (1970)
Snyder, S. H.: Amphetamine psychosis: A “model” schizophrenia mediated by dopamine. Amer. J. Psychiat. 130, 61–67 (1974)
Taylor, K. M., Snyder, S. H.: Differential effects of d- and l-amphetamine on behavioral and on catecholamine disposition in dopamine and norepinephrine containing neurons of the rat brain. Brain Res. 28, 295–309 (1971)
Thornburg, J. E., Moore, K. E.: Dopamine and norepinephrine uptake by brain synaptosomes: Relative inhibitory potencies of l- and d-amphetamine and amantadine. Rsch. Comm. Chem. Path. Pharm. 5, 81–89 (1973)
Von Kamnen, D., Murphy, D. L.: Attenuation of the euphoriant and activating effects of d- and l-amphetamine by lithium carbonate treatment. Psychopharmacologia (Berl.) 44, 215–224 (1976)
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This research was begun when both authors were associated with the Illinois State Psychiatric Institute
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Smith, R.C., Davis, J.M. Comparative effects of d-amphetamine, l-amphetamine and methylphenidate on mood in man. Psychopharmacology 53, 1–12 (1977). https://doi.org/10.1007/BF00426687
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DOI: https://doi.org/10.1007/BF00426687