The concept of pharmacologic cocaine interception as a treatment for drug abuse.
Cocaine access to brain tissue and associated cocaine-induced behaviors are substantially reduced in rats and mice by significant plasma levels of an enzyme that rapidly metabolizes the drug. Similar results have been obtained in rodents and humans with therapeutic anti-cocaine antibodies, which sequester the drug and prevent its entry into the brain. We show that an efficient cocaine hydrolase can lead to rapid unloading of anti-cocaine antibodies saturated with cocaine, and we provide a theoretical basis for the hypothesis that dual therapy with antibody and hydrolase enzyme may be especially effective.
Gao
Yang
Y
Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Orson
Frank M
FM
Kinsey
Berma
B
Kosten
Tom
T
Brimijoin
Stephen
S
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000276:immunology* / Q000378:metabolism*; D004359:Drug Therapy, Combination; D006801:Humans; D006867:Hydrolases / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006868:Hydrolysis; D051379:Mice; D051381:Rats; D012201:Reward; D019966:Substance-Related Disorders / Q000188:drug therapy*
D000906:Antibodies; D006867:Hydrolases; D003042:Cocaine