Hyperthermic and lethal effects of methamphetamine: Roles of dopamine D1 and D2 receptors

Ito, Miki; Numachi, Yohtaro; Ohara, Arihisa; Sora, Ichiro

doi:10.1016/j.neulet.2008.04.034

Cited by 14 publications

(16 citation statements)

References 12 publications

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“…The major presenting symptom in emergency rooms involving a METH overdose is extreme hyperthermia that can be lethal if left untreated (Bowyer et al, 1984; Ito et al, 2008). Other presenting symptoms commonly observed, particularly in high-dose patients, include hypertension, tachycardia, dyspnea, and chest pain, with other features including increased agitation, altered mental status, pupil dilation, shivering, and possible seizure activity (Albertson et al, 1999).…”

Section: Clinical Pharmacology and Considerations Related To Meth mentioning

confidence: 99%

“…Consequently, pharmacological and molecular manipulations involving these systems have long been a focus in characterizing the nature of METH-induced hyperthermia (e.g., Ito et al, 2008; Makisumi et al, 1998; Metzger et al, 2000). Concurrently, the ability of many drugs with no recognized monoaminergic actions (e.g., pentobarbital, MK-801, ethanol, dantrolene) to successfully block METH hyperthermia (Makisumi et al, 1998; Miller & O’Callaghan, 1994) underscores the complexities involved in determining and understanding the mechanisms involved in METH-induced hyperthermia.…”

Section: Pharmacological and Molecular Biological Studies Of Meth mentioning

confidence: 99%

“…METH fails to elicit hyperthermia in dopamine D 2 knockout mice (Ito et al, 2008; Granado et al, 2011). Likewise, the dopamine D 2 antagonists, haloperidol and sulpiride, attenuate METH-induced hyperthermia in mice (Funahashi et al, 1990; Albers & Sonsalla, 1995).…”

Section: Pharmacological and Molecular Biological Studies Of Meth mentioning

confidence: 99%

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Methamphetamine-induced toxicity: An updated review on issues related to hyperthermia

Matsumoto

Seminerio

Turner

et al. 2014

Pharmacology & Therapeutics

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Reports of methamphetamine-related emergency room visits suggest that elevated body temperature is a universal presenting symptom, with lethal overdoses generally associated with extreme hyperthermia. This review summarizes the available information on methamphetamine toxicity as it pertains to elevations in body temperature. First, a brief overview of thermoregulatory mechanisms is presented. Next, central and peripheral targets that have been considered for potential involvement in methamphetamine hyperthermia are discussed. Finally, future areas of investigation are proposed, as further studies are needed to provide greater insight into the mechanisms that mediate the alterations in body temperature elicited by methamphetamine.

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Section: Clinical Pharmacology and Considerations Related To Meth mentioning

confidence: 99%

Section: Pharmacological and Molecular Biological Studies Of Meth mentioning

confidence: 99%

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Methamphetamine-induced toxicity: An updated review on issues related to hyperthermia

Matsumoto

Seminerio

Turner

et al. 2014

Pharmacology & Therapeutics

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“…49 In addition, CNS-controlled mechanisms that are specific to the control of temperature are critical. 50 However, Dopamine receptor antagonists 3,13 , which are effective in controlling hyperthermia in some models, have an action on motor activity. 51 The mechanisms by which NAC affect peripheral and central pathways, remains to be addressed.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that activation of particular dopamine receptors in the central nervous system (CNS) mediates, at least partially, drug-induced hyperthermia, 3,13 suggesting that dopamine-blocking neuroleptic drugs may be helpful. 3,10,13 However, the role of peripheral thermogenic sites has thus far being under-appreciated. The correlation between increased core body temperature and high motor activity has led to the hypothesis that muscle activity is a source of heat in drug abuse.…”

Section: Introductionmentioning

confidence: 99%

Reactive oxygen species scavenger N-acetyl cysteine reduces methamphetamine-induced hyperthermia without affecting motor activity in mice

et al. 2014

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Hyperthermia is a potentially lethal side effect of Methamphetamine (Meth) abuse, which involves the participation of peripheral thermogenic sites such as the Brown Adipose Tissue (BAT). In a previous study we found that the anti-oxidant N-acetyl cysteine (NAC) can prevent the high increase in temperature in a mouse model of Meth-hyperthermia. Here, we have further explored the ability of NAC to modulate Meth-induced hyperthermia in correlation with changes in BAT. We found that NAC treatment in controls causes hypothermia, and, when administered prior or upon the onset of Meth-induced hyperthermia, can ameliorate the temperature increase and preserve mitochondrial numbers and integrity, without affecting locomotor activity. This was different from Dantrolene, which decreased motor activity without affecting temperature. The effects of NAC were seen in spite of its inability to recover the decrease of mitochondrial superoxide induced in BAT by Meth. In addition, NAC did not prevent the Meth-induced decrease of BAT glutathione. Treatment with S-adenosyl-L-methionine, which improves glutathione activity, had an effect in ameliorating Meth-induced hyperthermia, but also modulated motor activity. This suggests a role for the remaining glutathione for controlling temperature. However, the mechanism by which NAC operates is independent of glutathione levels in BAT and specific to temperature. Our results show that, in spite of the absence of a clear mechanism of action, NAC is a pharmacological tool to examine the dissociation between Meth-induced hyperthermia and motor activity, and a drug of potential utility in treating the hyperthermia associated with Meth-abuse.

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Methamphetamine-induced lethal toxicity in zebrafish larvae

et al. 2022

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Hyperthermic and lethal effects of methamphetamine: Roles of dopamine D1 and D2 receptors

Cited by 14 publications

References 12 publications

Methamphetamine-induced toxicity: An updated review on issues related to hyperthermia

Methamphetamine-induced toxicity: An updated review on issues related to hyperthermia

Reactive oxygen species scavenger N-acetyl cysteine reduces methamphetamine-induced hyperthermia without affecting motor activity in mice

Methamphetamine-induced lethal toxicity in zebrafish larvae

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