Progress in neuro-psychopharmacology最新文献

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 phloretin-sensitive component of lithium (Li⁺) efflux from erythrocytes has been reported to be significantly reduced in patients with bipolar affective disorders. The value of this finding depends on how reproducible the efflux measurements are. We have therefore investigated the intra-individual day-to-day reproducibility of this parameter, and total erythrocyte Li⁺ efflux in patients with bipolar affective disorders and in age and sex matched healthy controls.

2. Six carefully selected, typical bipolar patients and age and sex matched healthy volunteers were studied. These experiments were repeated under identical conditions on 3 occasions within a brief time period (21 days).

3. We have found that both the total erythrocyte Li⁺ efflux and the phloretin-sensitive Li⁺ efflux exhibited considerable day-to-day intra-individual variability in both patients and healthy controls. The standard deviation of total efflux values was as large as ± 31.1% of the mean in some subjects. Mean phloretin-sensitive Li⁺ efflux for patients was found to be 0.066 ± 0.02 mEq/1 RBC, and for controls 0.048 ± 0.01 mEq/1 RBC, in agreement with values reported in the literature. However, in some individuals standard deviation of this parameter, was as high as ± 50% of the mean. This variation was not the result of the biochemical technique, since all measurements were carried out in duplicate, and these differed less than 5%.

4. These findings suggest, that in view of the small absolute values of the phloretin-sensitive Li⁺ efflux, and its considerable day-to-day variation, the relevance of this biochemical parameter to the postulated cell membrane defect in affective disorders should be interpreted with some caution and needs further evaluation.

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. 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. 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.

1. Eight normal male volunteers were tested under eight different treatment conditions: amoxapine 50 and 100 mg, amitriptyline 50 mg. and placebo—each condition with and without ethanol—(1.3 g/kg body weight), utilizing a double-blind repeated measures latin square design balanced for carry-over. Motor reflex, pursuit rotor and depth perception tests were conducted when blood levels of the active drugs and alocohol were simultaneously at or near peak.

2. Analyses revealed significant effects of amitriptyline and ethanol on the motor reflex and pursuit rotor but not for depth perception tests, and the effects of ethanol appeared to be potentiated by amitriptyline on the pursuit rotor test; this was not true for amoxapine.

3. Although the effects of 100 mg of amoxapine were consistently greater than for 50 mg or placebo, these differences did not reach a statistical significant level.

4. Since amoxapine did not differ significantly from placebo, these results suggest that the effects of amoxapine on driving skills may not be as pronounced as those produced by amitriptyline.

1. Experimental rats were chronically treated with haloperidol and tested with dopaminergic and cholinergic drugs for their anorexic effects.

2. All of the test drugs significantly reduced the compulsive eating that results from food deprivation.

3. Chronic haloperidol failed to change sensitivity of the animals to dopaminergic or cholinergic drugs. There was a trend towards an increase in sensitivity to a peripheral effect of a cholinergic drug.

4. In contrast to the present data, sensitivity to dopaminergic drugs in producing locomotor stimulation and stereotypy is increased after chronic haloperidol. These experiments suggest that alteration in neurotransmitter functioning after chronic neuroleptics markedly differs in different neurobehavioral systems.

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.