title: Development of an anti-cotinine vaccine to potentiate nicotine-based smoking cessation strategies.
abstract: Nicotine replacement therapies (NRT) have limited success in smoking cessation. The efficacy of nicotine may be compromised by its main metabolite, cotinine. An anti-cotinine vaccine to remove this antagonism could enhance the efficacy of NRT. We show that cotinine is a weak nicotinic agonist and decreases responses to nicotine, consistent with antagonism through receptor desensitisation. trans-4-Thiol cotinine was coupled to tetanus toxoid, and rats immunised repeatedly. Vaccination raised antibodies specific for cotinine that do not recognise other metabolites or nicotine. Increased serum cotinine concentrations following nicotine administration indicate sequestration of cotinine by antibodies, encouraging further evaluation of this vaccine in behavioural models of nicotine addiction and relapse.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Oliver
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Pashmi
authors.forename: Paul
authors.initials: P
authors.lastname: Barnett
authors.forename: Pascal
authors.initials: P
authors.lastname: Mettens
authors.forename: Ralph
authors.initials: R
authors.lastname: Biemans
authors.forename: Philippe
authors.initials: P
authors.lastname: Monteyne
authors.forename: Rémi
authors.initials: R
authors.lastname: Palmantier
authors.forename: Timothy
authors.initials: T
authors.lastname: Gallagher
authors.forename: Sharn
authors.initials: S
authors.lastname: Ramaya
authors.forename: Susan
authors.initials: S
authors.lastname: Wonnacott
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003367:Cotinine / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D016540:Smoking Cessation / Q000379:methods*; D018074:Vaccines, Conjugate / Q000302:isolation & purification*
chemical_list: D011978:Receptors, Nicotinic; D018074:Vaccines, Conjugate; D009538:Nicotine; D003367:Cotinine; D004298:Dopamine