[Classification and determination of the pharmacodynamics of a new tetracyclic antidepressive agent, pirlindol, using pharmaco-EEG and psychometry].
In a double-blind placebo-controlled study the encephalotropic and psychotropic properties of a new tetracyclic pyrazino-indole derivative were studied in 10 normal volunteers. They received, randomized at weekly intervals, single oral doses of placebo, 75 mg, 150 mg and 225 mg pirlindol, as well as 75 mg imipramine, 20 mg tranylcypromine and 150 mg nomifensine as reference drugs. Pharmaco-EEG, psychometric and physiological data were obtained at the hours 0, 1, 2, 4, 6 and 8 after oral administration. Digital computer period analysis of the EEG demonstrated moderate CNS effects with pirlindol as compared with placebo. Its pharmaco-EEG profile, especially after higher dosage (150 and 225 mg), was characterized by a decrease in delta and theta activity, an increase in alpha activity and a delta and theta activity, an increase in alpha activity and a decrease in beta activity, as well as by an attenuation of the average frequency and frequency deviation and a trend towards an augmentation of the amplitude and amplitude variability. This profile is typical for antidepressants of the desipramine type and was also observed in our present study after 150 mg nomifensine and (although less markedly) and 20 mg tranylcypromine. 75 mg pirlindol induced, however, changes characterized by a concomitant increase in slow and superimposed fast activities and by a decrease in alpha activity. These alterations were described previously as typical for antidepressants of the imipramine type, and were also noted after 75 mg imipramine in the present study. Time-efficacy calculations showed the maximal pharmacodynamic effect of pirlindol in the 4th to 6th hour, of 75 mg imipramine in the 2nd hour, of 20 mg tranylcypromine in the 4th hour and of 150 mg nomifensine in the 6th hour. Dose/treatment-efficacy calculations identified in the 1st and 2nd hour post drug 75 mg imipramine as the most CNS-effective drug, in the 4th and 6th hour 150 mg pirlindol and in the 8th hour 225 mg pirlindol. Psychometric investigations showed only slight changes after pirlindol, reaching only rarely the level of statistical significance (improvement in attention after 225 mg pirlindol, decrease in tapping after 75 and 150 mg pirlindol, as well as attenuation of the complex reaction after all 3 doses of pirlindol). Concentration, attention-variability, psychomotor activity, CFF, after effect (Archimedean spiral), reaction time, mood and affectivity were not significantly altered as compared with placebo. Pulse, systolic and diastolic blood pressure did not show any clinical relevant changes either.(ABSTRACT TRUNCATED AT 400 WORDS)
D000328:Adult; D000928:Antidepressive Agents; D001143:Arousal / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004569:Electroencephalography; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D006334:Heart Function Tests; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D010919:Placebos; D011594:Psychometrics; D011600:Psychopharmacology; D011930:Reaction Time; D012016:Reference Values; D014191:Tranylcypromine / Q000494:pharmacology
D000928:Antidepressive Agents; D002227:Carbazoles; D010919:Placebos; D009627:Nomifensine; D014191:Tranylcypromine; D007099:Imipramine; C009830:pirlindole
Klassifikation und Bestimmung der Pharmakodynamik eines neuen tetrazyklischen Antidepressivums, Pirlindol, mittels Pharmako-EEG und Psychometrie.