A novel injectable solution could reverse the effects of an otherwise lethal overdose of cocaine in an emergency setting, according to a new study.

Researchers at the Scripps Research Institute (La Jolla, CA, USA) developed the antidote, a ready-made solution of antibodies that works as a passive vaccine, much like those used to treat snakebite, using a genetically engineered mouse to produce antibodies against cocaine. The best of these antibodies, called GNCgzk, showed ten times the cocaine-binding affinity of GNC92H2, a molecule developed by the same team in 2005 in a murine model. The drug-specific antibodies swiftly remove cocaine from the bloodstream, reducing direct effects on the heart and nearby organs. In addition, since the cocaine molecules are also small enough to cross the blood-brain barrier (BBB), the sudden lowering of bloodstream concentration causes them to diffuse rapidly out of brain tissue, protecting the brain.

4In a preliminary test, the scientists showed that an injection of GNCgzk antibodies 30 minutes before an injection of a lethal cocaine dose greatly reduced the signs of overdose--such as awkward movements and seizures--and kept all treated mice alive. By contrast, about half of untreated mice and 15% of GNC92H2-treated mice died. In another test that better simulated a real-life emergency situation, mice were first given a cocaine overdose, and three minutes later were infused with GNCgzk. About half of untreated mice were killed by such a dose, GNC92H2 reduced that rate to about 28%, and the new GNCgzk antibodies reduced the mortality rate further, to 20%.

More strikingly, a stripped-down version of GNCgzk dubbed F(ab')2-gzk, which contains only the antibody's cocaine-binding segments, reduced the mortality to zero, as well as significantly reducing overdose signs such as seizures. The researchers are now trying to find ways to produce the F(ab')2-gzk antidote economically and in large quantities. Such a treatment could be useful not only in reducing the immediate effects of an overdose, but also in preventing near-term relapses. It could be administered to patients in addiction recovery or detoxification programs as a prophylactic treatment to supplement other medications, such as antidepressants, and counseling. The study was published in the April 2012 issue of Molecular Pharmaceutics.

“This would be the first specific antidote for cocaine toxicity,” said senior author Kim Janda, PhD, a professor in the department of immunology and microbial science. “It's a human antibody so it should be relatively safe, it has a superior affinity for cocaine, and we examined it in a cocaine overdose model that mirrors a real-life scenario.”

http://www.gzjiayumed.com/en/index.asp