Alcohol-induced organic cerebral psychosyndromes: partial reversal of cognitive impairments assisted by dihydroergocristine.

Chronic alcohol abusers show a specific pattern of cerebral damage associated with cognitive and behavioral defects known as the organic cerebral psychosyndrome, which is partially reversible upon discontinuation of ethanol consumption. To assess the potential of nootropic drug therapy in alcohol rehabilitation in a double-blind study design, 56 consecutive patients who participated in routine rehabilitation therapy received 2 x 3 mg/day dihydroergocristine or placebo in tablet form over 6-13 weeks. Forty-nine patients completed the protocol. Although significant improvement was seen in both groups, we could document a specific cognitive restitution effect attributable to dihydroergocristine. Significant differences in favor of the active drug group were demonstrated by Mini-Mental State Examination, Syndrome Brief Test, Paired Words Test, in the neuropsychiatric Brief Cognitive Rating Scale assessments, and in the Clinical Global Impression of Change rating. No significant between-group differences were found in the Digit Symbol Test and the Block Design Test as well as in the Brief Psychiatric Rating Scale (BPRS). Dihydroergocristine was equivalent to placebo in terms of subjective drug tolerance, lack of side effects, and laboratory parameters. Based on this profile of efficacy and safety, we recommend dihydroergocristine as an adjuvant drug in alcohol rehabilitation.

Amantadine versus biperiden: a double-blind study of treatment efficacy in neuroleptic extrapyramidal movement disorders.

Anticholinergic treatment of neuroleptic extrapyramidal movement disorders (EPS) has been associated with induction of tardive dyskinesia. Also an increasing abuse of anticholinergics by schizophrenic patients is noted. Since as early as 1976, positive effects of amantadine (AMA) on neuroleptic EPS have been described, therefore a controlled study of these reports seemed worthwhile. Forty-two schizophrenic patients (of which 7 were dropouts) of three centers entered the study and were treated for EPS in a double-blind design: 18 (11 m, 7 f) with AMA and 17 (8 m, 9 f) with biperiden (BIP). Identical preparations of AMA 100 mg, tid) and BIP (2 mg, tid) were used in treatment of haloperidol-induced EPS (AMA, mean 22.4 mg haloperidol; BIP, mean 19.6 mg haloperidol). Effects of treatment and possible side effects were rated: EPS for the intensity of EPS, BPRS for quantification of psychotic symptoms, FSUCL for rating the side effects and KUSTA to document patients' mood. Ratings were recorded on days 0, 3, 7, 14, 28 and at discontinuation, respectively. All patients were treated with haloperidol and levomepromazine (for tranquilization/sleep induction) and the respective antiparkinsonian agent for 14 days. Patient characteristics did not differ significantly in either groups. In the AMA treatment group, 2 patients dropped out for noncompliance, in the BIP group, 5 (3 no effect, 1 noncompliance, 1 agitation). All results as recorded with the different rating instruments showed a significant (p < 0.01) overall improvement, whereas no significant differences between treatment groups could be determined, notably the treatment effect of both drugs on EPS was similar. Thus, the application of AMA in cases of neuroleptic EPS seems justified and is a useful alternative of anticholinergic drugs. Certain advantageous aspects of AMA treatment of EPS with regard to the glutamate hypothesis of schizophrenia and tardive dyskinesia are discussed.

Pharmacokinetic and -dynamic studies with a new anxiolytic, suriclone, utilizing EEG mapping and psychometry.

1. In a double-blind, placebo-controlled, cross-over study, acute pharmacokinetic, neurophysiological and psychotropic effects of suriclone, a new cyclopyrrolone derivative, were investigated and compared with alprazolam. 2. Fifteen normal young volunteers received randomized oral single doses of placebo, 0.1, 0.2 and 0.4 mg suriclone as well as 1 mg alprazolam as reference compound. Investigations were carried out before and 1, 2, 4, 6 and 8 h after drug administration. 3. Pharmacokinetic investigations by radioimmunoassay showed a dose-dependent fast rise of plasma concentrations with a peak at 1 h and a rapid decline thereafter. Both the Cmax and the AUC values exhibited a linear relationship to dose. 4. EEG brain mapping demonstrated significant CNS effects of both compounds, characteristic for tranquillizers (increase of beta, decrease of alpha and increase of delta activity; attenuation of total power and acceleration of the centroid, i.e. centre of gravity frequency). When compared with alprazolam, suriclone exerted less sedative effects. 5. Time-efficacy calculations showed the pharmacodynamic peak effect of suriclone from the 2nd to the 4th hour, and of alprazolam in the 1st hour. Dose-efficacy calculations showed that the most pronounced CNS changes occurred after 1 mg alprazolam, followed by 0.4, 0.2 and 0.1 mg suriclone. 6. Psychometric investigations demonstrated no significant effects after the two lower doses of suriclone, while 0.4 mg and 1 mg alprazolam induced a decrement both in noopsychic and thymopsychic variables seen after higher doses of anxiolytic sedatives. Psychophysiology (critical flicker fusion, pupillometry, and skin conductance measures) pulse rate, systolic and diastolic blood pressure remained unchanged. 7. Psychophysiology (critical flicker fusion, pupillometry and skin conductance measures) showed differential dose-dependent effects. Pulse rate, systolic and diastolic blood pressure remained unchanged. Anxiolytic-characteristic side-effects (tiredness, drowsiness, etc.) occurred predominantly after the highest doses 0.4 mg suriclone and 1 mg alprazolam.

[Relation between blood levels and average quantitative EEG and psychometrically assessed pharmacodynamic changes following zotepine]. / Zur Beziehung zwischen Blutspiegeln und mittels quantitativem EEG und Psychometrie gemessenen pharmakodynamischen Veränderungen nach Zotepin.

In a double-blind, placebo-controlled study, the relationships between blood levels and pharmacodynamics of zotepine were investigated in 15 healthy subjects. They received randomized at weekly intervals single oral doses of 25, 50 and 100 mg zotepine and 50 mg clozapin as reference substance. Blood sampling for zotepine and prolactin plasma levels, quantitative EEG analyses, psychometry and tolerability measures were carried out at the hours 0, 1, 2, 4, 6 and 8. There was a dose-dependent increase in zotepine plasma levels with a tmax between 2-4 hours post-drug and cmax: 6.9, 14.8 and 19.6 ng/ml for the 3 doses, respectively and a slow decline thereafter. Prolactin levels also rose dose dependently, peaking in the 4th hour. Regression and correlation analyses demonstrated: the higher the zotepine plasma levels, the more delta/theta, the less alpha activity and the slower the centroid in the spectral analysed EEG and the more decrease in reaction time performance, numerical memory and CFF in psychometry. Neurophysiological changes started at 8 ng/ml, psychometric ones at 9 ng/ml. Our pharmacodynamic findings suggested zotepine to be a sedative broad-band neuroleptic, which was also reflected in the side effects.