Gas chromatographic behaviour and pharmacological activity of neuroleptica

Biological activity in vitro, quantified as equilibrium inhibition constants to the dopamine receptor, of a series of neuroleptica are correlated with parameters describing polar and apolar interactions of these molecules with the receptor. Gas-chromatographic retention indices on stationary phases of different polarity are compared with parameters that are classically used in such quantitative structure/activity studies. To describe a polar interactions, a series of classical parameters such as several valence molecular indices and log k′ in a reversed-phase h.p.l.c. system are included; retention indices on the apolar stationary phase, OV101, are used as the gas-chromatographic (g.c.) parameter. To take the more specific polar interactions into account, quantum-chemical charge parameters such as the dipole moment and the charge on atoms directly involved in the interaction were calculated. Retention indices on the more polar phase OV17 are taken as the g.c. parameter for polar interactions. It is shown that the retention indices on OV101 can replace classical parameters describing aspecific or apolar interactions. The retention indices of OV17 do not correlate with biological activity and are worse than the charge parameters.