Conformational requirements for antibody recognition of fluphenazine and the thermodynamics of the binding processes

Abstract An antiserum raised to a fluphenazine-like immunogen shows great specificity for phenothiazines carrying 2-trifluoromethyl substituents. Specificity is also preferentially shown for molecules having aminopropyl side-chains which are covalently orientated towards the C-2 substituents on the heterocyclic nucleus, thus suggesting that a preferred conformation of fluphenazine and similar drug molecules exists in solution in which the side-chain is associated with the C-2 substituent and is thereby selectively recognized by the specific antibodies. The thermodynamics of the interactions between fluphenazine and the antiserum at different pH's indicates that the binding processes are directly related to the degree of ionization of the piperazine side-chain, being mainly ionic at pH 6.0 and mainly hydrophobic at pH 9.0. The significance of these results with respect to proposed models for the interactions between fluphenazine and dopaminergic receptors in the brain is discussed.