Effects of a Long-acting Mutant Bacterial Cocaine Esterase on Acute Cocaine Toxicity in Rats

Overview

Journal Drug Alcohol Depend

Publisher Elsevier

Specialty Psychiatry

Date 2011 Apr 13

PMID 21481548

Citations 10

Authors

Gregory T Collins

Matthew E Zaks

Alyssa R Cunningham

Carley St Clair

Joseph Nichols

Diwahar Narasimhan

Mei-Chuan Ko

Roger K Sunahara

James H Woods

Affiliations

Soon will be listed here.

Abstract

Background: A longer acting, double mutant bacterial cocaine esterase (CocE T172R/G173Q; DM CocE) has been shown to protect mice from cocaine-induced lethality, inhibit the reinforcing effects of cocaine in rats, and reverse cocaine's cardiovascular effects in rhesus monkeys. The current studies evaluated the effectiveness of DM CocE to protect against, and reverse cocaine's cardiovascular, convulsant, and lethal effects in male and female rats.

Methods: Pretreatment studies were used to determine the effectiveness and in vivo duration of action for DM CocE to protect rats against the occurrence of cardiovascular changes, convulsion and lethality associated with acute cocaine toxicity. Posttreatment studies were used to evaluate the capacity of DM CocE to rescue rats from the cardiovascular and lethal effects of large doses of cocaine. In addition, male and female rats were studied to determine if there were any potential effects of sex on the capacity of DM CocE to protect against, or reverse acute cocaine toxicity in rats.

Results: Pretreatment with DM CocE dose-dependently protected rats against cocaine-induced cardiovascular changes, convulsion and lethality, with higher doses active for up to 4h, and shifting cocaine-induced lethality at least 10-fold to the right. In addition to dose-dependently recovering rats from an otherwise lethal dose of cocaine, post-treatment with DM CocE also reversed the cardiovascular effects of cocaine. There were no sex-related differences in the effectiveness of DM CocE to protect against, or reverse acute cocaine toxicity.

Conclusions: Together, these results support the development of DM CocE for the treatment of acute cocaine toxicity.

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References

Koehler S, Ladham S, Rozin L, Shakir A, Omalu B, Dominick J . The risk of body packing: a case of a fatal cocaine overdose. Forensic Sci Int. 2005; 151(1):81-4. DOI: 10.1016/j.forsciint.2004.07.005. View

Brimijoin S, Gao Y, Anker J, Gliddon L, Lafleur D, Shah R . A cocaine hydrolase engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and reinstatement of drug seeking in rats. Neuropsychopharmacology. 2008; 33(11):2715-25. PMC: 2562914. DOI: 10.1038/sj.npp.1301666. View

Brody S, Slovis C, Wrenn K . Cocaine-related medical problems: consecutive series of 233 patients. Am J Med. 1990; 88(4):325-31. DOI: 10.1016/0002-9343(90)90484-u. View

Landry D, Zhao K, Yang G, Glickman M, Georgiadis T . Antibody-catalyzed degradation of cocaine. Science. 1993; 259(5103):1899-901. DOI: 10.1126/science.8456315. View

MENDELSON J, Mello N, Sholar M, Siegel A, Kaufman M, Levin J . Cocaine pharmacokinetics in men and in women during the follicular and luteal phases of the menstrual cycle. Neuropsychopharmacology. 1999; 21(2):294-303. DOI: 10.1016/S0893-133X(99)00020-2. View

Sun H, Pang Y, Lockridge O, Brimijoin S . Re-engineering butyrylcholinesterase as a cocaine hydrolase. Mol Pharmacol. 2002; 62(2):220-4. DOI: 10.1124/mol.62.2.220. View

Blaho K, Logan B, Winbery S, Park L, Schwilke E . Blood cocaine and metabolite concentrations, clinical findings, and outcome of patients presenting to an ED. Am J Emerg Med. 2000; 18(5):593-8. DOI: 10.1053/ajem.2000.9282. View

Przywara D, Dambach G . Direct actions of cocaine on cardiac cellular electrical activity. Circ Res. 1989; 65(1):185-92. DOI: 10.1161/01.res.65.1.185. View

Tella S, Korupolu G, Schindler C, Goldberg S . Pathophysiological and pharmacological mechanisms of acute cocaine toxicity in conscious rats. J Pharmacol Exp Ther. 1992; 262(3):936-46. View

10.

Mittleman M, Mintzer D, Maclure M, Tofler G, Sherwood J, Muller J . Triggering of myocardial infarction by cocaine. Circulation. 1999; 99(21):2737-41. DOI: 10.1161/01.cir.99.21.2737. View

11.

McCord J, Jneid H, Hollander J, de Lemos J, Cercek B, Hsue P . Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Circulation. 2008; 117(14):1897-907. DOI: 10.1161/CIRCULATIONAHA.107.188950. View

12.

Mello N, Bowen C, Mendelson J . Comparison of plasma cocaine levels during a "binge" pattern of cocaine administration in male and female rhesus monkeys. Psychopharmacology (Berl). 2002; 164(1):19-26. DOI: 10.1007/s00213-002-1188-x. View

13.

Carroll M, Gao Y, Brimijoin S, Anker J . Effects of cocaine hydrolase on cocaine self-administration under a PR schedule and during extended access (escalation) in rats. Psychopharmacology (Berl). 2010; 213(4):817-29. PMC: 3631565. DOI: 10.1007/s00213-010-2040-3. View

14.

Cooper Z, Narasimhan D, Sunahara R, Mierzejewski P, Jutkiewicz E, Larsen N . Rapid and robust protection against cocaine-induced lethality in rats by the bacterial cocaine esterase. Mol Pharmacol. 2006; 70(6):1885-91. DOI: 10.1124/mol.106.025999. View

15.

Haney M, Kosten T . Therapeutic vaccines for substance dependence. Expert Rev Vaccines. 2004; 3(1):11-8. DOI: 10.1586/14760584.3.1.11. View

16.

Pitts D, Udom C, Marwah J . Cardiovascular effects of cocaine in anesthetized and conscious rats. Life Sci. 1987; 40(11):1099-111. DOI: 10.1016/0024-3205(87)90573-x. View

17.

Halter J, Gordon S, Smith M, Terry L . Role of the central nervous system in hemodynamic and sympathoadrenal responses to cocaine in rats. J Pharmacol Exp Ther. 1990; 255(1):154-60. View

18.

Pan Y, Gao D, Yang W, Cho H, Yang G, Tai H . Computational redesign of human butyrylcholinesterase for anticocaine medication. Proc Natl Acad Sci U S A. 2005; 102(46):16656-61. PMC: 1283827. DOI: 10.1073/pnas.0507332102. View

19.

Morishima H, Abe Y, Matsuo M, Akiba K, Masaoka T, Cooper T . Gender-related differences in cocaine toxicity in the rat. J Lab Clin Med. 1993; 122(2):157-63. View

20.

Collins G, Brim R, Narasimhan D, Ko M, Sunahara R, Zhan C . Cocaine esterase prevents cocaine-induced toxicity and the ongoing intravenous self-administration of cocaine in rats. J Pharmacol Exp Ther. 2009; 331(2):445-55. PMC: 2775252. DOI: 10.1124/jpet.108.150029. View