ArticlesA Nicotine Conjugate Vaccine Reduces Nicotine Distribution to Brain and Attenuates Its Behavioral and Cardiovascular Effects in Rats
Section snippets
Drugs and Reagents
(−)-Nicotine bitartrate, (−)-cotinine, (−)-methyl-3H-nicotine 81 Ci/mmol, and goat anti-IgG-peroxidase conjugate were obtained from Sigma Chemical Co. (St. Louis, MO). Internal standards for the nicotine/cotinine assay were a gift form Dr. Peyton Jacob. (−)-Nicotine-N-oxide was a gift from Professor John Gorrod. Nicotine was administered to rats as nicotine bitartrate, but all doses and measured concentrations are expressed as the base.
Synthesis of Immunogen
The hapten trans-3′-aminomethylnicotine was prepared by
Experiment 1. Effects of Nic–IgG (Passive Immunization) on the Distribution of a Single Dose of Nicotine
The ability of pretreatment with Nic-IgG to bind nicotine in serum and reduce nicotine distribution to the brain was evaluated.
Discussion
Most existing or candidate treatments for drug abuse target brain receptors or neurotransmitter pathways. Because these targets also mediate normal brain function, side effects and lack of specificity are common. Drug-specific antibodies can bind drug outside of the central nervous system, reducing drug acces to receptor sites 12, 31. This peripheral site of action, as well as the high specificity of antibody-drug binding, makes the use of drug-specific antibodies potentially attractive as an
Acknowledgements
This work was supported by NIDA Grant DA10714 (P.R.P.) and grants from Nabi (D.H.M., P.R.P.).
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