PII-35.

Background/aims: Tobacco extract and smoke condensate are complex natural mixtures showing biological activities. Nicotinic receptors are known to be involved in the self-medication behaviour observed in schizophrenia patients. We use the bioaffinity screening technology, i.e. nicotinic receptors immobilized on stationary phases, to screen tobacco smoke for unknown ligands.Methods: Membrane α3β4-subtype nicotinic receptors are expressed in HEK-293 cells, partly purified and immobilized on artificial membranes silica-based stationary phase (IAM-PCDD2, Regis Technologies®). Binding properties of columns are characterized by frontal chromatography. Tobacco extracts are injected and retained compounds are directed to a second analytical column, connected to a suitable detector for structural identification.Results: Preliminary results show that columns effectively bind nicotinic ligands. HPLC fingerprinting of the hydrophilic/cationic fraction of smoke condensate show a large proportion of nicotine that can flaw binding of minor ligands. Nicotine imprinted chromatography has been tested to solve this problem by selectively removing the nicotine of the extract. Binding capacity of the columns is of critical importance.Conclusions: The ability of bioaffinity chromatography to identify ligands in a mixture by an on-line process is promising for the drug discovery of drugs acting as receptor agonists, competitive and non-competitive antagonists.Clinical Pharmacology & Therapeutics (2005) 79, P45–P45; doi: 10.1016/j.clpt.2005.12.160 [ABSTRACT FROM AUTHOR]