Antagonism of Intravenous Cocaine Lethality in Nonhuman Primates

Guinn, Meredith M.; Bedford, John A.; Wilson, Marvin C.

doi:10.3109/15563658008989979

Cited by 86 publications

(21 citation statements)

References 1 publication

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“…Seizures stopped within two minutes after administration of diazepam. These findings agree with those of Guinn et al (49) who found diazepam i.v. prevented seizures and death in monkeys given cocaine by continuous infusion.…”

Section: Discussionsupporting

confidence: 81%

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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Section: Discussionsupporting

confidence: 81%

Diazepam Protects Against the Enhanced Toxicity of Cocaine Adulterated With Atropine

et al. 2008

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“…Although it may seem intuitive that the optimal pharmacological approach to the patient with hypertension and tachycardia in the setting of catecholamine excess would involve the use of a b-adrenoceptor antagonist, sound animal and human research demonstrates the catastrophic risks that serve as the basis for the absolute contraindication attached to the use of b-adrenergic receptor antagonists in the setting of cocaine toxicity [57][58][59][60][61]. To summarize, b-adrenergic receptor antagonists exacerbate coronary vasoconstriction, are unpredictable at controlling blood pressure and contribute to lethality in both animals and humans.…”

Section: Treatment Of Arrhythmias Resulting From Cocaine-associated Cmentioning

confidence: 99%

Treatment of patients with cocaine‐induced arrhythmias: bringing the bench to the bedside

Hoffman

2010

Brit J Clinical Pharma

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Widespread use of cocaine and its attendant toxicity has produced a wealth of benchwork studies and small animal investigations that evaluated the effects of cocaine on the cardiovascular system. Despite this wealth of knowledge, very little is known about the frequency or types of arrhythmias in patients with significant cocaine toxicity. The likely aetiologies; catecholamine excess, sodium channel blockade, potassium channel blockade, calcium channel effects, or ischaemia may act alone or in concert to produce a vast array of clinical findings that are modulated by hyperthermia, acidosis, hypoxia and electrolyte abnormalities. The initial paper in the series by Wood & Dargan providing the epidemiological framework of cocaine use and abuse is followed by a detailed review of the electrophysiological effects of cocaine by O'Leary & Hancox. This review is designed to complement the previous papers and focuses on the diagnosis and treatment of patients with cocaine‐associated arrhythmias.

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“…In animal models of cocaine toxicity, sedation with a benzodiazepine increases the mean lethal and convulsive doses of cocaine (Guinn et al, 1980) and improves survival (Guinn et al, 1980;Catravas and Waters, 1981;Yuksel et al, 2013). Through their action on the g-aminobutyric acid receptors in the amygdala and reticular activating system, benzodiazepines function as anxiolytics, sedatives, and antiepileptics.…”

Section: Benzodiazepinesmentioning

confidence: 99%

Experimental Treatments for Cocaine Toxicity: A Difficult Transition to the Bedside

Connors

Hoffman

2013

J Pharmacol Exp Ther

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Antagonism of Intravenous Cocaine Lethality in Nonhuman Primates

Cited by 86 publications

References 1 publication

Diazepam Protects Against the Enhanced Toxicity of Cocaine Adulterated With Atropine

Diazepam Protects Against the Enhanced Toxicity of Cocaine Adulterated With Atropine

Treatment of patients with cocaine‐induced arrhythmias: bringing the bench to the bedside

Experimental Treatments for Cocaine Toxicity: A Difficult Transition to the Bedside

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