Evaluation of the anticocaine monoclonal antibody GNC92H2 as an immunotherapy for cocaine overdose.
The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.
Carrera
M Rocío A
MR
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road (BCC 582), La Jolla, CA 92037, United States. rcarrera@scripps.edu
Trigo
José Manuel
JM
Wirsching
Peter
P
Roberts
Amanda J
AJ
Janda
Kim D
KD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000276:immunology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose / Q000401:mortality / Q000628:therapy; D007167:Immunotherapy / Q000379:methods; D008297:Male; D051379:Mice; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D015996:Survival Rate; D013997:Time Factors
D000911:Antibodies, Monoclonal; D003042:Cocaine