Antagonism of the neurotoxicity due to a single administration of methylenedioxymethamphetamine

Schmidt, Christopher J.; Black, Christine K.; Taylor, Vicki L.

doi:10.1016/0014-2999(90)90245-2

Cited by 77 publications

(39 citation statements)

References 29 publications

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“…Schmidt et al (1990b) did not measure body temperature but Hewitt & Green (1994) observed that the combination of haloperidol and MDMA, whilst not producing hypothermia, did markedly attenuate the hyperthermia normally produced by the drug, an observation also con®rmed by the present study. We therefore repeated the experiment on the neuroprotective e ect of haloperidol but used a homeothermic blanket, thereby keeping the rectal temperature of the animals elevated to a similar level to that seen in the group given only MDMA (Figure 1).…”

Section: Discussionsupporting

confidence: 84%

“…Both Schmidt et al (1990b) and Hewitt & Green (1994) have reported that administration of haloperidol concurrently with MDMA attenuates the neurodegeneration of 5-HT terminals in the brain produced by this neurotoxic amphetamine and this observation was con®rmed by the current study. Schmidt et al (1990b) did not measure body temperature but Hewitt & Green (1994) observed that the combination of haloperidol and MDMA, whilst not producing hypothermia, did markedly attenuate the hyperthermia normally produced by the drug, an observation also con®rmed by the present study.…”

Section: Discussionsupporting

confidence: 81%

“…For example Stone et al, (1988) proposed a role for dopamine based on their studies which showed that the long term depletion of cerebral 5-HT which follows administration of MDMA was attenuated by the dopamine synthesis inhibitor a-methyl p-tyrosine or the monoamine depletor reserpine. Schmidt et al (1990b) reported that injection into the striatum of the selective dopamine neurotoxin 6-hydroxydopamine (6-OHDA) blocked the neurotoxic e ects of MDMA on 5-HT neurones not only in the striatum but also other forebrain regions such as the hippocampus and cortex. In addition Stone et al (1988) reported that the dopamine uptake inhibitor GBR 12909 was neuroprotective.…”

Section: Introductionmentioning

confidence: 99%

“…In addition Stone et al (1988) reported that the dopamine uptake inhibitor GBR 12909 was neuroprotective. Finally, both Schmidt et al (1990b) and Hewitt & Green (1994) have shown that acute administration of the dopamine antagonist haloperidol together with MDMA provides e ective protection against neurotoxic damage. It is acknowledged that none of these studies demonstrate authoritatively the involvement of dopamine in the MDMAinduced neurodegeneration because none of the compounds used in these investigations (haloperidol, 6-OHDA, a-methyl p-tyrosine) selectively alter dopamine function.…”

Section: Introductionmentioning

confidence: 99%

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Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration

Colado

O’Shea

Granados

et al. 1999

British J Pharmacology

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1 We investigated whether dopamine plays a role in the neurodegeneration of 5-hydroxytryptamine (5-HT) nerve endings occurring in Dark Agouti rat brain after 3,4-methylenedioxymethamphetamine (MDMA or`ecstasy') administration. 2 Haloperidol (2 mg kg 71 i.p.) injected 5 min prior and 55 min post MDMA (15 mg kg 71 i.p.) abolished the acute MDMA-induced hyperthermia and attenuated the neurotoxic loss of 5-HT 7 days later. When the rectal temperature of MDMA+haloperidol treated rats was kept elevated, this protective e ect was marginal. 3 MDMA (15 mg kg 71 ) increased the dopamine concentration in the dialysate from a striatal microdialysis probe by 800%. L-DOPA (25 mg kg 71 i.p., plus benserazide, 6.25 mg kg 71 i.p.) injected 2 h after MDMA (15 mg kg 71 ) enhanced the increase in dopamine in the dialysate, but subsequent neurodegeneration was unaltered. L-DOPA (25 mg kg 71 ) injected before a sub-toxic dose of MDMA (5 mg kg 71 ) failed to induce neurodegeneration. 4 The MDMA-induced increase in free radical formation in the hippocampus (indicated by increased 2,3-and 2,5-dihydroxybenzoic acid in a microdialysis probe perfused with salicylic acid) was unaltered by L-DOPA. 5 The neuroprotective drug clomethiazole (50 mg kg 71 i.p.) did not in¯uence the MDMA-induced increase in extracellular dopamine. 6 These data suggest that previous observations on the protective e ect of haloperidol and potentiating e ect of L-DOPA on MDMA-induced neurodegeneration may have resulted from e ects on MDMA-induced hyperthermia. 7 The increased extracellular dopamine concentration following MDMA may result from e ects of MDMA on dopamine re-uptake, monoamine oxidase and 5-HT release rather than aǹ amphetamine-like' action on dopamine release, thus explaining why the drug does not induce degeneration of dopamine nerve endings.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration

Colado

O’Shea

Granados

et al. 1999

British J Pharmacology

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“…Schmidt et al [21] suggest that dopamine receptor antagonists (e.g. haloperidol) or inhibitors of dopamine synthesis (e.g.…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia associated with 3,4‐methylenedioxyethamphetamine (‘Eve’)

1993

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SummaryA patient was admitted kith hyperthermia, muscle rigidity, rhabdomyolysis and disseminated intravascular coagulation. He was initially thought to have taken 3.4-methylenedioxymethamphetamine ( M D M A . 'Ecstasy'), but subsequent toxicology revealed the presence of 3.4-methylenedioxyethamphetarnine (MDEA, 'Eve'), its sister drug, in his blood. Subsequent in vitro testing for malignant hyperthermia proved to be negative.

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Addition of a 5-HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP-CIT binding to dopamine transporters in rat frontal cortex and hippocampus

Reneman

Bruin

Lavalaye

et al. 2001

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Antagonism of the neurotoxicity due to a single administration of methylenedioxymethamphetamine

Cited by 77 publications

References 29 publications

Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration

Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration

Hyperthermia associated with 3,4‐methylenedioxyethamphetamine (‘Eve’)

Addition of a 5-HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP-CIT binding to dopamine transporters in rat frontal cortex and hippocampus

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