title: Nicotine hapten structure, antibody selectivity and effect relationships: results from a nicotine vaccine screening procedure.
abstract: The aim of the present study was to synthesise and screen a set of novel nicotine hapten immunogens used for the treatment of nicotine dependence. In the screening process we studied the amount of antibodies generated and their selectivity, using ELISA techniques, and their effects on nicotine-induced dopamine release in the NAC(shell) of the rat, assessed by in vivo voltammetry. We conclude that even small changes such as the linker attachment on the nicotine molecule as well as the structure of the linker may greatly influence the selectivity of the antibodies and the central neurobiological effects of nicotine that are considered critical for its dependence producing properties.
authors.affiliation: Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden. Electronic address: Sabina.de.Villiers@ki.se.
authors.forename: Sabina H L
authors.initials: SHL
authors.lastname: de Villiers
authors.affiliation: Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Lindblom
authors.affiliation: Organic Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Genadiy
authors.initials: G
authors.lastname: Kalayanov
authors.affiliation: Organic Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Organic Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Ivan
authors.initials: I
authors.lastname: Baraznenok
authors.affiliation: Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Malmerfelt
authors.affiliation: Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Marcus
authors.affiliation: Organic Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Anette M
authors.initials: AM
authors.lastname: Johansson
authors.affiliation: Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden.
authors.forename: Torgny H
authors.initials: TH
authors.lastname: Svensson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D008297:Male; D015394:Molecular Structure; D009538:Nicotine / Q000737:chemistry / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D019966:Substance-Related Disorders / Q000628:therapy*; D014612:Vaccines / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D006241:Haptens; D014612:Vaccines; D009538:Nicotine; D004298:Dopamine