Progress in neuro-psychopharmacology最新文献

1. An electron-capture gas chromatographic procedure for the simultaneous quantitation of urinary levels of amines of psychiatric interest has been developed.

2. The amines were isolated from urine using a liquid ion exchanger, then acetylated and perfluoroacylated for analysis. This procedure improved extraction efficiency and analytical sensitivity.

3. The developed procedure was rapid, simple, specific and sensitive.

4. Urinary levels of 5-hydroxytryptamine, 3-methoxytyramine, normetanephrine, 2-phenylethylamine, tryptamine, $\text{m}$- and $\text{p}$-tyramine in control subjects were determined using this analytical procedure and agreed with literature values.

1. The ability of three ‘trace’ amines, namely 2-phenylethylamine (PEA), $\text{p}$-tyramine ($\text{p}$-TA) and tryptamine (T) to facilitate the release of radiolabelled dopamine (DA) from prisms of rat striatum was investigated. At concentrations of 1.0 μM and 10 μM, all three amines caused a significant increase in DA release when compared to controls. The order of strength for this effect was $\text{p}$-TA > PEA > T

2. The addition of an α-methyl group on T caused a significant increase in its ability to release DA.

3. The introduction of nomifensine, a drug which blocks carrier-mediated transport of DA, into the superfusion medium dramatically reduced the amount of DA released from the prisms by the trace amines.

1. The alcohol field is presently in ideological crisis.

2. Traditional concepts of alcohol problems, most notably the ideas of Alcoholics Anonymous and Jellinek's disease concept, were not empirically based but nevertheless led to societal recognition of alcohol problems as serious health problems.

3. Recent governmental support for alcohol research has generated a substantial body of scientific knowledge, much of which contradicts traditional ideas.

4. Consequently, the field is undergoing a paradigm shift that will have far-reaching practical implications.

1. To determine the efficacy and safety of maprotiline (Ludiomil) in children with functional enuresis and behavioural disorders, 12 patients (mean age, 9 yrs 4 mos) participated in an open trial consisting of baseline evaluations (4 weeks) followed by maprotiline therapy (8 weeks) and post-drug follow-up (4 weeks). Nine of these patients had moderate or greater degrees of behavioural problems; in 5 enuresis appeared resistant to previous antienuretic medication. Two patients had encopresis.

2. Evaluations included paediatric and psychiatric assessments; parents' ratings of behaviour, enuresis and sleep; clinical laboratory tests; EKGs and measurements of vital signs. The initial daily dose of maprotiline was 10 mg, the maximum 75 mg, and the mean during the final week 63 mg.

3. Compared to baseline, with maprotiline therapy enuresis improved in 11 patients (range 7–100%; mean, 32%) and worsened in one (25%). Encopresis significantly improved in 2 patients. Clinical global improvement was marked in 3 patients, moderate in 6, slight in 2, and absent in one. Clinical and parents' assessments indicated improvements of hyperkinetic, conduct and sleep problems.

4. Adverse effects were infrequent and mild. Heart rate and blood pressure means slightly increased with maprotiline, but all vital signs and EKGs remained within normal limits. Maprotiline was well tolerated and accepted.

5. Four weeks following maprotiline withdrawal, there was further improvement of enuresis in 4 patients and of behaviour in 2, enuresis relapsed in 6 patients and behaviour in 5, while behaviour was unchanged in 5 patients.

6. Our data suggest that maprotiline is effective and safe in the therapy of children with enuresis and behaviour disorders. Controlled trials are indicated.

1. A single injection of fluphenazine decanoate (FD) antagonized effects of acute d-amphetamine (2.5 mg/kg) for a variable period of time (4 to 28 days), depending upon the dosage of the neuroleptic used (2.5 or 5.0 mg/kg) and the behavioural parameter(s) monitored.

2. Locomotion and rearing were antagonized for a longer duration than was sniffing. Normal locomotor response to amphetamine was attained 12 and 28 days following the administration of 2.5 and 5.0 mg/kg FD, respectively. However, the 2.5 mg/kg FD group displayed significantly more locomotor activity on days 20 and 24 post-treatment. A similar supersensitive response was not demonstrable with the higher dose of FD (5.0 mg/kg), or with the other behavioural measures.

3. The prompt and pronounced elevation of serum prolactin in response to the neuroleptic returned to within the normal range by days 4 and 14, following administration of 2.5 and 5.0 mg/kg FD, respectively.

4. These results indicate that the behavioural paradigm is more sensitive in monitoring the effects of FD and could serve as a useful model in investigating the dose- and time-related effects of other long-acting neuroleptics.

1. Two levels of task complexity were used to determine the degree to which pimozide, a DA receptor blocker, influenced performance on a conditional discrimination task.

2. Pigeons were trained on a simultaneous matching-to-sample task. On behalf the trials they were required to peck the side key that was the same color as the center key (identity matching). For the remaining trials subjects were presented with a symbolic matching procedure—red was correct when the sample was a vertical line and green was correct for a horizontal line. When performance was stable all subjects received four doses of pimozide i.m. (vehicle, 0.05, 0.15 and 0.45 mg/kg) according to a Latin Square sequence.

3. Pimozide increased response latencies and decreased rates of responding. Accuracy of responding on identity trials was not altered by pimozide while it was decreased on symbolic matching trials.

4. It was concluded that (a) highly complex tasks are more sensitive to the effects of pimozide than are simple tasks, and (b) dopaminergic systems may be involved in the maintenance of complex learned behavior.

1. Mental performance of patients with artificial pacemakers was found to be impaired when the heart rate was lowered from 70 to 45 beats per minute in sitting position.

2. The same lowering of the heart rate caused less impairment in supine body position.

3. These findings are discussed with regard to cerebral blood flow; the impairment of performance at the lower heart rate being interpreted as caused by cerebral hypoxia.

4. Under the same conditions Piracetam seems to have an effect which not only counteracts hypoxia, but also brings about enhancement of performance in some other way.

5. The above mentioned findings seem to manifest themselves in EEG's evaluated by means of Spectral Parameter Analysis.

1. Dopamine (D₂-type) receptors were solubilized from striatum of three species (human, canine, calf) using digitonin.

2. The receptors were labeled with ³H-spiperone and assayed by Sephadex G-50 columns or polyethylene glycol precipitation.

3. The soluble receptors from canine and human tissue had similar K_d's and rank order of drug affinities to the membrane-bound sites.

4. Soluble calf receptors showed reduced affinity for spiperone and chlorpromazine (12-fold). Non-specific binding also increased.

5. Solubilized canine binding was insensitive to ascorbate, Mn⁺⁺, and ethylenediamine tetracetic acid (EDTA) in contrast to the membrane binding sites.

6. Solubilized canine striatum serves as an excellent source of D₂ receptors because these receptors are stable in solution and are a prototype of human D₂ receptors.