Development of an anti-cotinine vaccine to potentiate nicotine-based smoking cessation strategies.
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.
Oliver
Jennifer L
JL
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Pashmi
Ghazaleh
G
Barnett
Paul
P
Mettens
Pascal
P
Biemans
Ralph
R
Monteyne
Philippe
P
Palmantier
Rémi
R
Gallagher
Timothy
T
Ramaya
Sharn
S
Wonnacott
Susan
S
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*
D011978:Receptors, Nicotinic; D018074:Vaccines, Conjugate; D009538:Nicotine; D003367:Cotinine; D004298:Dopamine