Acute cocaine toxicity: The effect of agents in non-seizure-induced death

Tseng, Chui Chung; Derlet, Robert W.; Albertson, Timothy E

doi:10.1016/0091-3057(93)90317-m

Cited by 23 publications

(11 citation statements)

References 27 publications

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“…The benzodiazepine diazepam blocked cocaine-induced convulsions but only minimized paroxysmal activity and partially prevented the lethal effects of cocaine. 18,27 Similarly, in the present study, the short acting-benzodiazepine, midazolam, eliminated overt convulsions and dramatically lessened seizurogenic activity, without completely preventing lethality. The glutamate N -methyl- d -aspartate receptor antagonist MK801 (dizocilpine) and valproic acid also minimized cocaine-induced convulsions but did not alter lethality.…”

Section: Discussionsupporting

confidence: 75%

“…High doses of cocaine produce overt behavioral convulsions and simultaneous epileptogenic activity in animals and humans. 4,18–23 In the current study, the effects of CocE on cocaine-induced convulsions, electroencephalographic (EEG) activity, and lethality were evaluated by telemetry measurements in freely moving rats. EEG activity was evaluated in addition to overt behavioral convulsions to assess any potential nonconvulsive seizure activity that could be occurring with or instead of convulsions.…”

Section: Introductionmentioning

confidence: 99%

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A Bacterial Cocaine Esterase Protects Against Cocaine-Induced Epileptogenic Activity and Lethality

Jutkiewicz

Baladi

Cooper

et al. 2009

Annals of Emergency Medicine

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Study objective Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Methods Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. Results The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (−)-2β-carbomethoxy-3β-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. Conclusion The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

A Bacterial Cocaine Esterase Protects Against Cocaine-Induced Epileptogenic Activity and Lethality

Jutkiewicz

Baladi

Cooper

et al. 2009

Annals of Emergency Medicine

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“…We established the dosages of cocaine and atropine (40 + 20 and 40 + 60) tested here on the basis of the proportion found in human intoxication, adapted to rats; when the drugs were given singly as one dose, they caused no seizure or death. This is in agreement with other reports where the psychostimulant, given acutely by the same route, produced seizures and death in Sprague-Dawley rats, starting from 100 mg / kg (10,13,26,27). However, in our experiments cocaine increased spontaneous motor activity, body temperature, MAP, and HR, indicating a certain efficacy.…”

Section: Discussionsupporting

confidence: 80%

Diazepam Protects Against the Enhanced Toxicity of Cocaine Adulterated With Atropine

et al. 2008

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Abstract. We examined the toxicity of cocatropine (cocaine / atropine mixture) and the therapeutic potential of diazepam on some behavioral and physiological parameters in rats. Atropine (20 and 60 mg / kg) or cocaine (40 mg / kg) alone did not induce any seizure or death, but the combination significantly increased both, after both acute and binge treatment. There was a significant increase of EEG mean total spectral power in cocatropine-in comparison with cocaine-treated animals. Hyperlocomotion was observed in non-seizuring rats treated with cocaine or cocatropine. Cocaine, atropine 60, and cocatropine (40 + 20 and 40 + 60) all induced hyperthermic effects in non-seizuring rats, while cocatropine (40 + 60)-seizuring animals had hypothermia. An initial hypertensive and tachycardiac effect within 15 min was followed by a secondary fall in the cocatropine (40 + 60) group. Cocatropine toxicity was partially or fully reversed by diazepam (5 mg / kg), given intraperitoneally after the first seizure. The present findings provide, for the first time, details of a synergistic toxic effect of the cocaine / atropine mixture and of the potential of diazepam for treating cocatropine-related hospital emergencies.

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“…These data counteract our finding but one of the explanation of the discrepancies is that mGluR5 deletion produces adaptive changes in the central nervous system during brain development that may be responsible for the lack of differences in pharmacological response between mGluR5 knockout and wild-type animals to acute cocaine in adolescent mice. On the other hand, it is well known that in toxic (convulsant and lethal) effects of cocaine are involved receptor sites, such as serotoninergic, muscarinergic, as well as dopaminergic (Ritz and George 1993), or a 1 -adrenergic (Tseng et al 1993). Thus, further investigations will be required to elucidate the mechanism underlying the toxic effect of cocaine.…”

Section: Discussionmentioning

confidence: 94%

Pretreatment with Group I Metabotropic Glutamate Receptors Antagonists Attenuates Lethality Induced by Acute Cocaine Overdose and Expression of Sensitization to Hyperlocomotor Effect of Cocaine in Mice

Kotlińska

Bocheński

2009

Neurotox Res

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Cocaine abuse and dependence is a worldwide health problem. However, there are no currently approved medications to reduce cocaine abuse/relapse and toxicity. The aim of the present study was to test, whether group I metabotropic glutamate receptors (mGluRs) antagonists (mGluR1 and mGluR5) differentially regulate toxic versus behavioral effects of cocaine, both phenomena relevant to the psychopathology of cocaine addiction in humans. In the present study, we assessed the impact of mGluR1 antagonist-EMQMCM and mGluR5 antagonist-MTEP on the cocaine-induced lethality and the expression of sensitization to hyperlocomotor effect of cocaine in mice. Our study indicated that EMQMCM and MTEP, both substances at the doses of 5 and 10 mg/kg (but not 2.5 mg/kg), decreased cocaine-induced lethality produced by 75 mg/kg of cocaine, which was given acutely. The effect of EMQMCM was dose-dependent, and this compound at the dose of 10 mg/kg almost completely abolished the lethality induced by cocaine. MTEP reduced this cocaine effect at the doses of 5 and 10 mg/kg, equally. Furthermore, EMQMCM (1.25-5 mg/kg) at the doses of 2.5 and 5.0 mg/kg, and MTEP (2.5-10 mg/kg) only at the highest dose of 10 mg/kg, significantly reduced the expression of cocaine-induced (10 mg/kg) behavioral sensitization. Our results suggest that stimulation of mGluR1 and mGluR5 is involved in lethal effect of cocaine overdose and cocaine seeking behavior evaluated in behavioral sensitization test. However, the participation of mGluR1 in these cocaine effects seems to be dominant. Therefore, antagonists showing preferences towards mGluR1 might be useful in therapy of cocaine toxicity and abuse.

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Acute cocaine toxicity: The effect of agents in non-seizure-induced death

Cited by 23 publications

References 27 publications

A Bacterial Cocaine Esterase Protects Against Cocaine-Induced Epileptogenic Activity and Lethality

A Bacterial Cocaine Esterase Protects Against Cocaine-Induced Epileptogenic Activity and Lethality

Diazepam Protects Against the Enhanced Toxicity of Cocaine Adulterated With Atropine

Pretreatment with Group I Metabotropic Glutamate Receptors Antagonists Attenuates Lethality Induced by Acute Cocaine Overdose and Expression of Sensitization to Hyperlocomotor Effect of Cocaine in Mice

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