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Abstract

Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine.

C J Schmidt
Journal of Pharmacology and Experimental Therapeutics January 1987, 240 (1) 1-7;
C J Schmidt
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Abstract

The neurochemical effects of the unique psychedelic agent, methylenedioxymethamphetamine (MDMA), indicate it may be a serotonergic neurotoxin related to agents such as p-chloroamphetamine. MDMA had a biphasic effect on cortical serotonin concentrations beginning with an acute depletion of the transmitter which reached a maximum between 3 and 6 hr after drug administration. This early phase of depletion was reversible because cortical serotonin concentrations had recovered to control levels by 24 hr. However, transmitter concentrations were reduced significantly 1 week later, indicating a second phase of depletion. The latter phase of depletion was associated with a decrease in synaptosomal [3H]serotonin uptake due to a loss in the number of uptake sites with no change in the affinity of the carrier for serotonin. This neurotoxic effect of MDMA was found to be a property of the (+)-stereoisomer of the drug as only this enantiomer produced the depletion of cortical serotonin and the decrease in synaptosomal serotonin uptake at 1 week. In contrast to this, both stereoisomers of the drug could produce the acute depletion of cortical serotonin measured 3 hr after drug administration. Coadministration of the selective serotonin uptake inhibitor, fluoxetine, completely blocked the reduction in cortical serotonin concentrations 1 week after MDMA. Administration of fluoxetine at various times after MDMA revealed that the long-term effects of the drug developed independently of the acute depletion of serotonin and could be partially blocked by the uptake inhibitor as long as 6 hr after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 240, Issue 1
1 Jan 1987
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Abstract

Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine.

C J Schmidt
Journal of Pharmacology and Experimental Therapeutics January 1, 1987, 240 (1) 1-7;

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Abstract

Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine.

C J Schmidt
Journal of Pharmacology and Experimental Therapeutics January 1, 1987, 240 (1) 1-7;
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