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Amelioration of the acute cardiovascular effects of cocaine by a longer acting mutant cocaine esterase in freely moving rhesus monkeys
Author(s) -
Collins Gregory Thomas,
Carey Kathy Ann,
Ko MeiChuan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.764.5
Subject(s) - heart rate , blood pressure , saline , medicine , pharmacology , anesthesia
Cocaine is the most common illicit drug related to emergency room admissions, with the majority of visits due to cocaine‐associated chest pain resulting from increases in blood pressure (BP) and heart rate (HR). These studies were aimed at characterizing the capacity of a longer acting mutant form of cocaine esterase (T172R/G173Q; DM CocE) to ameliorate the cardiovascular effects of cocaine in four freely moving rhesus monkeys implanted with radio‐telemetric probes (DSI; D70‐PCT) capable of collecting continuous measures of BP and HR. DM CocE (0, 0.032, 0.1, 0.32, 1.0, or 3.2 mg/kg; IV) was administered 10 min after a dose of 3.2 mg/kg; IV cocaine (M2 was tested at 1.0 mg/kg; IV), and BP and HR were recorded for the 120 min following cocaine administration. DM CocE dose‐dependently, and rapidly decreased cocaine‐induced elevations in BP in each of the four monkeys, with saline‐like levels observed within the first 5 min. Similarly, DM CocE dose‐dependently decreased cocaine‐induced elevations in HR in three of the four monkeys, although over a slightly longer timecourse. These results suggest that DM CocE may provide a novel, and effective therapeutic for the treatment of acute cocaine toxicity. Supported by NIDA grant DA 023213