Determination of pharmacodynamics of the new neuroleptic zetidoline by neuroendocrinologic, pharmaco-EEG, and psychometric studies--Part I.
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. Plasma sampling for prolactin levels, EEG recording, evaluation of blood pressure, pulse and side effects were carried out at 0, 1, 2, 4, 6, and 8 h. Psychometric tests were done at 0, 2, 4, 6, and 8 h. The prolactin response to zetidoline proved to be dose-dependent and peaked within the first 2 h, whereas after 2 mg haloperidol, prolactin levels increased only as late as in the 6th and 8th h. This time course was similar to the neurophysiologic and psychometric ones. 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004569:Electroencephalography; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011388:Prolactin / Q000378:metabolism*; D011594:Psychometrics; D011597:Psychomotor Performance / Q000187:drug effects*; D011897:Random Allocation
D014150:Antipsychotic Agents; D007093:Imidazoles; C027277:zetidoline; D011388:Prolactin; D006220:Haloperidol