Effects of Salicylate on 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Neurotoxicity in Rats

Yeh, S.Y.

doi:10.1016/s0091-3057(97)90010-1

Cited by 27 publications

(19 citation statements)

References 43 publications

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“…Administration of sodium ascorbate or the antioxidant L-cysteine also prevents the long-term 5-HT depletions caused by MDMA exposure (Gudelsky, 1996) and another antioxidant, α-lipoic acid, pretreatment reduces 5-HT depletions in the hippocampus without preventing hyperthermia (Aguirre et al, 1999). Contrary to these findings, another study showed that salicylate does not prevent 5-HT terminal effects (Yeh, 1997). Although this one study may cast doubt on the role of free radical production in MDMA-induced 5-HT reductions, most of the evidence supports the concept of free radical damage.…”

Section: Adult Pharmacology Of ± 34-methylenedioxymethamphetaminementioning

confidence: 89%

Developmental effects of 3,4-methylenedioxymethamphetamine: a review

Skelton

Williams

Vorhees

2008

Behavioural Pharmacology

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Abstract± 3,4-Methylenedioxymethamphetamine (MDMA) is a chemical derivative of amphetamine that has become a popular drug of abuse and has been shown to deplete serotonin in the brains of users and animals exposed to it. To date, most studies have investigated the effects of MDMA on adult animals. With a majority of users of MDMA being young adults, the chances of the users becoming pregnant and exposing the fetuses to MDMA are also a concern. Evidence to date has shown that developmental exposure to MDMA results in learning and memory impairments in the Morris water maze, a task known to be sensitive to hippocampal disruption, when the animals are tested as adults. Developmental MDMA exposure leads to hypoactivity in the offspring as adults but does not affect outcome on tests of anxiety. MDMA administration decreases pup weight, increases corticosterone and brain-derived neurotrophic factor levels during treatment while decreasing brain levels of serotonin; a decrease that initially dissipates and then reappears in adulthood. Neonatal MDMA exposure increases the sensitivity of the serotonin 1A receptor, a possible mechanism underlying the learning and memory deficits seen. Taken together, the evidence shows that MDMA exposure has adverse effects on the developing brain and behavior. The animal and human data on developmental MDMA exposure are reviewed and their public health implications discussed.

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Section: Adult Pharmacology Of ± 34-methylenedioxymethamphetaminementioning

confidence: 89%

Developmental effects of 3,4-methylenedioxymethamphetamine: a review

Skelton

Williams

Vorhees

2008

Behavioural Pharmacology

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“…However, other recent data fail to support this contention (see below). Finally, Yeh (1997) reported that salicylate administration did not produce neuroprotection and suggested that MDMA-induced neurotoxicity might occur more through production of superoxides than hydroxyl radicals. However, these data are somewhat at variance with the other data presented above.…”

Section: Effects On Free Radical Production In the Brainmentioning

confidence: 99%

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

et al. 2003

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“…This protocol is more relevant for human conditions because MDMA is recreationally used in social settings associated with high arousal (eg, rave parties, music festivals). Third, in contrast to most studies, where a treatment drug was administered before or at the same time as MDMA (Yeh, 1997;Sprague et al, 2005;Shioda et al, 2008;Hysek et al, 2012;Taffe, 2012), we injected each of the three test drugs-clozapine, carvedilol, and labetalol-after the MDMA injection, when brain and body temperatures were already significantly increased (438°C). This dosing regimen closely mimics the clinical situation, in which MDMA-intoxicated patients are treated for pathological hyperthermia in hospital emergency rooms.…”

Section: Experimental Protocolmentioning

confidence: 99%

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction

Kiyatkin

Ren

Wakabayashi

et al. 2015

Neuropsychopharmacol

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MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (42.5°C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

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Effects of Salicylate on 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Neurotoxicity in Rats

Cited by 27 publications

References 43 publications

Developmental effects of 3,4-methylenedioxymethamphetamine: a review

Developmental effects of 3,4-methylenedioxymethamphetamine: a review

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction

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