Cardiovascular Effects of Cocaine in Squirrel Monkeys

Tella,; Cw, Schindler; Goldberg,

doi:10.1037/e496272006-007

Cited by 4 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In humans, the cardiovascular effects of cocaine are closely linked to circulating cocaine levels insofar as increases in MAP and HR appear shortly after use, and dissipate as cocaine is metabolized (e.g., Evans et al , 1996; Foltin et al , 1991; Javaid et al , 1978). Similar increases MAP and HR have been observed with cocaine in a variety species, including rats (e.g., Tella et al , 1991b; Tella et al , 1992), dogs (e.g., Wilkerson, 1988), and squirrel monkeys (e.g., Tella et al , 1990, 1991a). However, unlike what is observed in humans, the cardiovascular effects of cocaine in dogs and rats are much shorter-lived than the plasma cocaine levels.…”

Section: Discussionsupporting

confidence: 52%

Amelioration of the Cardiovascular Effects of Cocaine in Rhesus Monkeys by a Long-Acting Mutant Form of Cocaine Esterase

Collins

Carey

Narasimhan

et al. 2011

Neuropsychopharmacol

View full text Add to dashboard Cite

A long-acting mutant form of a naturally occurring bacterial cocaine esterase (T172R/G173Q CocE; DM CocE) has previously been shown to antagonize the reinforcing, convulsant, and lethal effects of cocaine in rodents. However, the effectiveness and therapeutic characteristics of DM CocE in nonhuman primates, in a more clinically relevant context, are unknown. The current studies were aimed at 1) characterizing the cardiovascular effects of cocaine in freely moving rhesus monkeys, 2) evaluating the capacity of DM CocE to ameliorate these cocaine-induced cardiovascular effects when administered 10 minutes after cocaine, and 3) assessing the monkeys’ immunologic responses to DM CocE following repeated administration. Intravenous administration of cocaine produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR) that persisted throughout the two-hour observation period following a dose of 3.2 mg/kg cocaine. Cocaine failed to produce reliable changes in ECG parameters, body temperature, and locomotor activity. DM CocE produced a rapid and dose-dependent amelioration of the cardiovascular effects, with saline-like MAP measures restored within 5 to 10 minutes, and saline-like HR measures restored within 20 to 40 minutes of DM CocE administration. Although administration of DM CocE produced increases in anti-CocE antibodies, they did not appear to have a neutralizing effect on the capacity of DM CocE to reverse the cardiovascular effects of cocaine. In conclusion, these findings in monkeys provide strong evidence to suggest that highly efficient cocaine esterases, such as DM CocE, can provide a potential therapeutic option for treatment of acute cocaine intoxication in humans.

show abstract