Psychostimulant-like effects of p-fluoroamphetamine in the rat

doi:10.1016/0014-2999(95)00478-5

European Journal of Pharmacology

Volume 287, Issue 2, 12 December 1995, Pages 105-113

https://doi.org/10.1016/0014-2999(95)00478-5 Get rights and content

Abstract

The present study was undertaken to compare the pharmacological properties of p-fluoroamphetamine with those of amphetamine and of other halogenated amphetamines, using several in vivo and in vitro tests. These included substitution testing in (+)-amphetamine (1 mg/kg, 5.4 μmol/kg, i.p.)-, (+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine [(+)-MBDB] (1.75 mg/kg, 7.18 μmol/kg, i.p.)-, and 5-methoxy-6-methyl-2-aminoindan (MMAI) (1.71 mg/kg, 8 μmol/kg, i.p.)-trained rats, [³H]5-HT and [³H]dopamine uptake inhibition in whole brain synaptosomes, and changes in striatal extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) as measured by in vivo microdialysis in freely moving rats. In drug discrimination substitution tests, p-fluoroamphetamine fully mimicked (+)-amphetamine (ED₅₀ 0.43 mg/kg, 2.11 μmol/kg), whereas ‘no substitution’ was observed in rats traincd to discriminate the serotonin (5-hydroxytryptamine, 5-HT)-releasing agents (+)-MBDB or MMAI from saline. p-Chloroamphetamine did not substitute for amphetamine but fully substituted for the (+)-MBDB and MMAI cues (ED₅₀ 0.17 mg/kg, 0.82 μmol/kg, and 0.14 mg/kg, 0.69 μmol/kg, respectively), p-Fluoroamphetamine, in comparison with p-chloroamphetamine and p-iodoamphetamine, showed much stronger inhibition of [³H]dopamine than [³H]5-HT uptake into rat brain synaptosomes but was less selective than amphetamine. p-Fluoroamphetamine (7.0 mg/kg, i.p.), 1 h after administration, strongly elevated (849% of baseline) extracellular dopamine in rat striatum measured using in vivo microdialysis. Amphetamine (2 mg/kg, i.p.) increased extracellular dopamine in rat striatum with a maximum at the same time as did p-fluoroamphetamine, but the latter gave a smaller increase. The data presented suggest that p-fluoroamphetamine resembles amphetamine more than it does the 5-HT-releasing type amphetamines.

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^a: Present address: Department of Pharmaceutical and Biomedical Sciences, Raabe College of Pharmacy, Ohio Northern University, Ada, OH 45810, USA.

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Regular paperPsychostimulant-like effects of p-fluoroamphetamine in the rat

Abstract

Structure-activity relationships in CF3 substituted phenethylamines

[3H]Cocaine binding and inhibition of [3H]dopamine uptake is similar in both the rat striatum and nucleus accumbens

Eur. J. Pharmacol.

A drug discrimination analysis of the lysergic acid diethylamide (LSD): in vivo agonist and antagonist effects of purported 5-hydroxytryptamine antagonists and of pirenpirone, a LSD-antagonist

J. Pharmacol. Exp. Ther.

Comparison of the discriminative stimulus properties of cocaine and amphetamine in rats

Br. J. Pharmacol.

6-Hydroxydopamine lesions of the nucleus accumbens attenuate the discriminative stimulus effects of d-amphetamine

Drug Dev. Res.

Structure-activity relationships among the halogenated amphetamines

Ann. NY Acad. Sci.

Influence of ring and side substituents on the selectivity of amphetamine as a monoamine oxidase inhibitor

Res. Commun. Subst. Abuse

Lowering of brain serotonin level by chloroamphetamines

Biochemical Pharmacol.

Comparison of 4-chloro-, 4-bromo- and 4-fluoroamphetamine in rats: drug levels in brain and effects on brain serotoninserotonim metabolism

Neuropharmacology

Effect of 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine on the depletion of brain serotonin by 4-chloroamphetamine

J. Pharmacol. Exp. Ther.

Reversible and irreversible phases of serotonin depletion by 4-chloroamphetamine

Eur. J. Pharmacol.

Role of dopamine D1 and D2 receptors in mediating the d-amphetamine discriminative cue

Eur. J. Pharmacol.

Biochemical pharmacology of the anorectic drug fenfluramine: a review

Curr. Med. Res. Opin.

Structure-activity studies on amphetamine analogs using drug discrimination methodology

Pharmacol. Biochem. Behav.

Regional studies of catecholamines in the rat brain. I. The disposition of [3H]-norepinephrine, [3H]-dopamine and [3H]DOPA in various regions of the brain

J. Neurochem.

A comparison of fenfluramine and amphetamine in man

Clin. Pharmacol. Ther.

p-Chloroamphetamine: Selective neurotoxic actions in brain

Science

Comparison between the neurotoxic and serotonin depleting effects of various halogenated derivatives of amphetamine in the rat

J. Pharmacol. Exp. Ther.

Role of dopamine of d-amphetamine-induced discriminative responding

Pharmacol. Biochem. Behav.

Stimulants as discriminative stimuli

[3H]Monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chioroamphetamine analogues

Eur. J. Pharmacol.

Synthesis and pharmacological examination ofexaminationof 1-(3-methoxy-4-methylphenyl)-2-aminopropane and 5-methoxy-6-methyl-2-aminoindan: similarities to 3,4-methylenedioxymeth-amphetamine (MDMA)

J. Med. Chem.

Drug discrimination by humans compared to nonhumans: current status and future directions

Psychopharmacology

Biochemical actions of amphetamine and other stimulants

A simplified method of evaluating dose-effect experiments

J. Pharmacol. Exp. Ther.

Regular paper
Psychostimulant-like effects of p-fluoroamphetamine in the rat

[³H]Cocaine binding and inhibition of [³H]dopamine uptake is similar in both the rat striatum and nucleus accumbens

Role of dopamine D₁ and D₂ receptors in mediating the d-amphetamine discriminative cue

Regional studies of catecholamines in the rat brain. I. The disposition of [³H]-norepinephrine, [³H]-dopamine and [³H]DOPA in various regions of the brain

[³H]Monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chioroamphetamine analogues