Pharmacopsychiatria最新文献

In the past, pharmacokinetics of benzodiazepines have been extensively described. However, knowledge about relationships between their plasma levels and pharmacodynamic effects are scanty. Therefore, we investigated under several experimental conditions the disposition and the psychological response of the short acting midazolam (single dose 0,075 mg/kg i.v. and 15 mg po) and of the moderate long acting oxazepam (30 mg/die for 5 days). Psychological and psychomotoric effects were evaluated by analogue scales (sedation index), d-2 letter cancellation test, reaction time, critical flicker fusion frequency and adjective mood list. In general, good correlations were found between those tests and plasma levels, especially for midazolam. Analogue scales and reaction-time proved to be most useful in our "effect-kinetic" approach.

The clinical significance of the high-affinity binding of psychotropic compounds to alpha 1-acid glycoprotein (alpha 1-AGP) in human serum has not been established yet. However, this binding may be of considerable theoretical interest since glycoproteins play a prominent role in the structure of cell membranes. In order to elucidate the nature of the binding to alpha 1-AGP several typical psychotropic compounds (diazepam, haloperidol, imipramine, perazine, phenobarbital and phenytoin) were investigated by means of equilibrium dialysis. The results suggest that among the classical CNS-drugs only those with a tricyclic structure are bound to two binding sites. Possible reason for the widely differing binding of a series of drugs are discussed in terms of their different chemical structure.

Siberian chipmunks (Eutamias sibiricus) were kept individually in small cages attached to a running wheel. Under continuous illumination of two different light intensities (0.4-0.9 lux and 400-1200 lux) the influence of Rolipram, a putative new antidepressant, on the period length tau was tested. Under both conditions Rolipram caused a lengthening of tau, a decrease of activity time alpha and an increase of rest time delta, resulting in a decrease of the alpha/delta ratio. These effects of Rolipram could be due to a slowing down of the circadian oscillatory system or an influence on the sensitivity towards light.

The effect of 1 mg dexamethasone on CSF levels of 5-hydroxyindoleacetic acid (5 HIAA), homovanillic acid (HVA) and cortisol (CS) was investigated in 100 psychiatric inpatients: 45 subjects had their lumbar punctures 1-4 days following dexamethasone administration, and the results were compared with those from 55 other patients investigated before drug ingestion. All patients were women, and none had received psychotropic medication for at least two weeks before the study. Seven subjects consented to two LPs both before and after dexamethasone. As expected, cortisol in the CSF significantly decreased after dexamethasone: the decrease was greatest 10 hours following the drug. HVA showed a weak and transient elevation after 10 hours only. CSF 5 HIAA was found to be significantly increased in postdexamethasone samples and high levels were still found even after 82 hours. Diagnostic differences (major or minor depression, schizophrenia, alcohol abuse or dependence) did not account for the observed differences. Repeated CSF examinations in seven subjects corroborated these findings: all cortisol values were decreased and all 5 HIAA values were increased after dexamethasone while HVA values showed random changes. The data may suggest that serotonergic mechanisms may be involved in dexamethasone action in the CNS. In addition, dexamethasone administration can alter CSF 5 HIAA level, a possible factor which should be taken into consideration in CSF studies.

Nine patients with endogenous depression have been treated with infusions of the synthetic methionine enkephaline analogue FK 33-824 for two days. Only on the first day acute effects on depressive symptoms could be observed. It cannot be decided if the observed mood alterations on the first treatment day are placebo effects. Depressive patients showed fewer adverse reactions than healthy volunteers. This might be explained by the previously described greater pain tolerance in depressives.

Seven patients with heroin addiction were hospitalized and immediately withdrawn from opiates. Abstinence symptomatology was evaluated quantitatively by use of the Himmelsbach Score. Maximal intensity of withdrawal symptomatology was reached within 2 days. beta-Endorphin immunoreactivity in plasma was measured by use of a very sensitive radioimmunoassay with a low cross-reactivity (28%) against beta-LPH. A statistically significant increase of mean plasma beta-endorphin-like immunoreactivity during withdrawal could be demonstrated.

1. The drug treatment of 1,263 psychiatric patients (= 96% of all in-patients admitted during a period of 2 years) was analyzed by means of case histories. During hospitalization 7.4% of all patients were treated completely drug-free; 12.5% received no psychoactive drugs. 2. The patients were hospitalized for 50 days on the average, and received psychoactive drugs on 43 days. During the total treatment period, they were prescribed an average of 4.3 (median 3.8) different drugs; of these, 2.7 (median 2.3) were various psychoactive drugs. Neuroleptics were the most frequently used drugs; they were prescribed at least once during treatment for 62% of all patients. Antidepressants were prescribed for almost 30% of the patients. 3. For the neuroleptics prescriptions decreased with patient's age; they increased for the antidepressants. Antiparkinsonian agents were prescribed to 51% of neuroleptic-treated patients under 45 years of age, and to 26% of these patients over 45. 4. Neuroleptics were prescribed more frequently in male patients, antidepressants in female patients. 5. Among the individual prescriptions, perazine was the most favoured of the neuroleptics, and amitriptyline of the antidepressants. Clozapine was prescribed for the longest period among all psychotropic agents except lithium salts. Antiparkinsonian agents were used for shorter periods than the neuroleptics administered simultaneously. One-fifth of the patients were given analgesics for brief periods. 6. Medication pattern is related to specific nosology. 95% of schizophrenic patients received neuroleptics for at least an average of 41 days; every second patient in this group received antiparkinsonian agents. 90% of unipolar depressed patients were given antidepressants; during one course of treatment at least 2 different antipressant drugs were prescribed for 32% of these patients. 43% of unipolar depressed patients received neuroleptics for an average of 33 days. Lithium salts were administered for an average of 45 days to 43% of the patients with affective disorders. 7. Treatment surveys of this kind supplement the collection of data on adverse drug reactions by drug monitoring systems. The relationship between the side effects of drugs and the prescription pattern of individual drugs allows one to determine the incidence rates of drug side effects.

In vivo turnover of NA in the brain is considerably high, but in vitro only a low activity of the enzyme DBH is detectable. It is supposed that this effect is brought about by endogenous enzyme inhibitors. It was demonstrated that the addition of rat brain homogenate, as well as different subcellular fractions from rat brain, inhibit the human serum DBH. Inhibitory activity is resistant to heat and acid but does not seem to be uniformly distributed within the cell. Pretreatment of brain homogenate with pronase reduced its inhibitory activity. In conclusion, pronase sensitive peptides are partially responsible for the inhibitory potency of tissue homogenates.

6 schizophrenic patients were treated in a cross-over design for 4 days each with 20 mg naloxone or placebo. No patient showed a significant change of his or her psychotic behaviour. This result is not in agreement with an antipsychotic action of the opiate antagonist.