Nicotine hapten structure, antibody selectivity and effect relationships: results from a nicotine vaccine screening procedure.
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.
de Villiers
Sabina H L
SHL
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.
Lindblom
Nina
N
Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden.
Kalayanov
Genadiy
G
Organic Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
Gordon
Sandra
S
Organic Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
Baraznenok
Ivan
I
Organic Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
Malmerfelt
Anna
A
Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden.
Marcus
Monica M
MM
Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden.
Johansson
Anette M
AM
Organic Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
Svensson
Torgny H
TH
Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Nanna Svartz väg 2, S-171 77 Stockholm, Sweden.
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*
D000906:Antibodies; D006241:Haptens; D014612:Vaccines; D009538:Nicotine; D004298:Dopamine