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Some neurochemical effects of amphetamine, methylamphetamine and p ‐bromomethylamphetamine in the rat
Author(s) -
LEONARD B. E.,
SHALLICE SUSAN A.
Publication year - 1971
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1971.tb08022.x
Subject(s) - amphetamine , dopamine , chemistry , reserpine , neurochemical , tyramine , medicine , pharmacology , endocrinology , serotonin , norepinephrine , stimulant , biochemistry , receptor
Summary1 Low doses of d ‐amphetamine increased brain noradrenaline concentrations in the rat; doses greater than 5 mg/kg, however, caused a decrease. Methylamphetamine also showed this dual effect, but a reduction in brain noradrenaline concentration only occurred when doses greater than 10 mg/kg were administered. p ‐Bromomethylamphetamine did not significantly reduce brain noradrenaline concentrations even at a dose of 60 mg/kg. The order of potency in reducing the concentration of noradrenaline correlated with the central stimulant effects; d ‐amphetamine produced the greatest and p ‐bromomethylamphetamine the least increase in motor activity. 2 d ‐Amphetamine and d ‐methylamphetamine potentiated the action of 4,α‐dimethyl‐ m ‐tyramine (H77/77) in depleting brain noradrenaline; the greatest potentiation was produced by d ‐amphetamine. This suggests that the phenylethylamines may affect brain noradrenaline concentrations by acting on the reserpine resistant uptake mechanism. 3 Differences were found in the effect of the three drugs on brain dopamine concentrations; d ‐amphetamine caused a decrease while p ‐bromomethylamphetamine caused an increase. Methylamphetamine had no effect on the concentration of dopamine. Only p ‐bromomethylamphetamine significantly reduced the depletion of brain dopamine concentrations caused by H77/77. 4 Methylamphetamine and p ‐bromomethylamphetamine reduced the concentration of 5‐hydroxytryptamine (5‐HT) in the brain; administration of the same dose of d ‐amphetamine did not change the concentration of 5‐HT. 5 Changes in the blood and brain concentrations of tyrosine and tryptophan, and in the concentration of γ‐amino‐ n ‐butyric acid in the brain could not be correlated with the changes observed in the concentrations of biogenic amines in the brain.