In a double-blind, placebo-controlled, crossover study, neuroendocrinologic, encephalotropic, and psychotropic effects of a new antidopaminergic compound zetidoline (DL 308) were investigated in ten healthy volunteers. In randomized sequences at weekly intervals they received single oral doses of placebo; 10, 20, and 40 mg zetidoline; and 2 mg haloperidol as positive control according to a Latin square design. Computer period analysis of the EEG demonstrated after 10, 20, and 40 mg zetidoline slight, marked, and moderate central nervous system (CNS) changes as compared with placebo, which were characterized by an increase of theta and also beta activity, decrease of alpha activity and average frequency (primary wave), and attenuation of the amplitude, indicating CNS-inhibitory effects. These inhibitory effects were more pronounced after the intermediate dosage. In the 6th and 8th h after the 10-mg dosage but also after the 40-mg dose some activating properties were observed, as indicated by the decrease in slow waves and increase in slow beta activity and average frequency.

[3H]Zetidoline has high affinity for striatal dopamine receptors. Its binding is saturable, stereo-specific, has a low non-specific component and is reversible and tissue specific. The Scatchard analysis gave a biphasic curve, indicating that [3H]zetidoline interacts with more than one population of receptor sites (B'max = 67 fmol mg-1 protein, K'd = 0.11 nM; B"max = 500 fmol mg-1 protein, K'd = 2.49 nM).