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Biomedical subjects

T Silverstone

Publications and source records attributed to T Silverstone.

At least 91 records · Page 5Linked to original sources
PubMed1984

Electrophysiological and haemodynamic changes with trazodone, amitriptyline and placebo in depressed out-patients.

Fourteen out-patients with major depressive disorder completed a double-blind, randomized, parallel group study using trazodone (n = 6), amitriptyline (n = 5) and matching placebo (n = 3). The average daily doses used were 223 mg and 95.3 mg for trazodone and amitriptyline, respectively, over the 28-day treatment period. Cardiovascular function was monitored with high speed ECG and by determining systolic time intervals. No significant effects of either drug on supine or standing blood pressure were demonstrated. Trazodone increased QTc on Day 1 only, and reduced heart rate and increased the PR interval on Day 15; these effects had disappeared by Day 29. Amitriptyline markedly increased heart rate, PR interval and QTc, and reduced T wave amplitude on Days 15 and 29. Trazodone had no consistent effect on systolic time intervals except to increase the LVET index, whereas amitriptyline increased both PEP index and PEP/LVET ratio on Days 15 and 29. It is concluded that amitriptyline had a much more marked effect on cardiac function than did trazodone.

Adult↗
PubMed1984

Zetidoline, a new antipsychotic. First controlled trial in acute schizophrenia.

Zetidoline (ZTD), a compound chemically unrelated to any available antipsychotic, with selective dopamine receptor-blocking properties, was compared with haloperidol (HLP) in a double-blind study on 56 in-patients who had either first episodes or acute relapses of schizophrenia. ZTD was found to be safe, as effective as HLP, and to produce significantly fewer extrapyramidal side-effects (EPS).

Acute Disease↗
PubMed1984

The clinical pharmacology of appetite suppressant drugs.

One way of gaining a greater understanding of the central mechanisms underlying hunger and the regulation of feeding behaviour in humans is to examine the actions and interactions on hunger and food intake of drugs with known or presumed pharmacological modes of action. To this end we have undertaken a number of studies which fall into three main categories: the mechanisms by which amphetamine anorexia is induced; the possible role of endogenous opioids in feeding; the action of amino acids thought to be involved in the regulation of feeding. In this field the potential for cross-fertilization between basic scientists working with laboratory animals and clinical scientists working with human subjects exists. For example, the clinical pharmacologist has been able to test out hypotheses on human subjects which could only have been developed using laboratory animals. Furthermore, using human subjects it is possible to extend the field of inquiry into an exploration of the subjective dimensions of appetite and hunger.

Animals↗
PubMed1983

Differential dose-response effects of dexamphetamine sulphate on hunger, arousal and mood in human volunteers.

The effect of dexamphetamine (d-Amp) and placebo on visual analogue scale (VAS) ratings of hunger, arousal and mood in nine male volunteers was observed. d-Amp (10 mg) significantly depressed hunger ratings but did not significantly affect arousal and mood ratings. d-Amp (20 mg) had a significant effect on all three ratings. There was a difference in the pattern of dose-response effects. Whereas 20 mg d-Amp produced greater changes than 10 mg in ratings of mood and arousal, there was no significant difference on ratings of hunger. These differences in dose-response relationships may reflect differences in the underlying neurochemical mechanisms mediating the stimulant and anorectic effects of d-Amp.

Adult↗
PubMed1983

Naloxone reduces the food intake of normal human volunteers.

While there is substantial evidence that the food intake of laboratory animals in suppressed following administration of opiate antagonists, there is less known about the effects of opiate antagonists on human feeding. This study was undertaken to examine the effect of the relatively specific opiate antagonist, naloxone, on the food intake of normal human volunteer subjects. We found that naloxone, given intravenously in single doses of 0.8 and 1.6 mg under double-blind conditions to 12 healthy subjects, caused a dose-related suppression of food intake compared to placebo, maximal at 2.5 h. No effect was observed on subjective ratings of hunger, satiety, mood or arousal, or on total flu id intake. These findings suggest that endogenous opiates may play a role in the regulation of human feeding.

Adult↗
PubMed1983

The clinical and psychometric evaluation of a new hypnotic drug, loprazolam, in general practice.

A double-blind crossover study was carried out in 16 patients with insomnia to assess the effectiveness and tolerance of a new hypnotic, loprazolam, with that of nitrazepam and placebo. Patients received 1 capsule each night for 7 days of either 1 mg loprazolam, 5 mg nitrazepam or placebo and then 7 days' treatment with each of the other medications in random order. The results of analogue rating scale assessment by the patients showed that 'ease of getting to sleep' and 'quality of sleep' were significantly better with loprazolam than with placebo. Loprazolam appeared to be at least as effective, if not more so, than nitrazepam. There were no significant differences between treatments on the morning muzziness assessment, which was low in each group, or in the psychometric tests carried out indicating that loprazolam is unlikely to produce hangover effects. There were no obvious differences between treatments in the incidence or frequency of side-effects spontaneously volunteered by the patients.

Adult↗
PubMed1982

Opiate mediation of amenorrhoea in hyperprolactinaemia and in weight-loss related amenorrhoea.

Endogenous opiates are involved in the control of pituitary gonadotrophin and PRL secretion, and possibly of food intake. Both hyperprolactinaemia and weight loss (especially in anorexia nervosa) are frequently associated with amenorrhoea and an absence of gonadotrophin pulsatility. Since it has been suggested that increased endogenous opiate tone may operate in both conditions, we infused high-doses of naloxone into twelve patients with amenorrhoea of whom five had hyperprolactinaemia and seven had weight-loss related amenorrhoea. Eleven of the twelve patients had low levels of oestradiol (less than 50 pmol/l). Naloxone induced a marked rise in both LH and FSH levels in all of the five hyperprolactinaemic patients. In contrast, the patients with weight-loss amenorrhoea responded to naloxone with only a small or no rise in gonadotrophins. There was no consistent change in PRL in either group of patients. It is concluded that in hyperprolactinaemia, but not weight-loss amenorrhoea, there is an important endogenous opiate-mediated tonic inhibition of secretion of hypothalamic gonadotrophin releasing hormone.

Adolescent↗
PubMed1982

Plasma prolactin and growth hormone levels in manic patients treated with pimozide.

During two weeks' treatment of 11 manic patients with pimozide there was close correspondence between the timecourse of improvement in clinical ratings and the rise in plasma prolactin between the second and fourteenth day. There were no significant differences in growth hormone levels during the manic episodes compared to recovery. These findings are discussed in relation to the role of dopamine in the release of prolactin and growth hormone, and in the pathogenesis of mania.

Adult↗
PubMed1981

Naloxone changes self-ratings but not performance in normal subjects.

The effects of single intravenous doses of naloxone (0.8 and 1.6 mg) in a variety of performance tasks and on subjective ratings of mood and bodily symptoms were investigated in 12 student volunteers. Naloxone was without effect on any of the performance measures. However, 5 min after naloxone (1.6 mg) the subjects felt significantly more troubled, mentally slow, incompetent, withdrawn and physically tired, and less irritable. These effects appeared to be dose-related since 0.8 mg produced similar, but not statistically significant changes. Sixty-five minutes after the higher dose subjects felt significantly more muzzy and incompetent; in contrast to the effects at 5 min they now felt significantly more irritable. These results are difficult to explain solely in terms of opiate receptor blockade.

Adult↗
PubMed1981

Double-blind comparative clinical trial of pimozide and chlorpromazine in mania. A test of the dopamine hypothesis.

Pimozide (PMZ), a relatively specific dopamine (DA) receptor blocking drug, was compared to chlorpromazine (CPZ) in a double-blind, between-patient clinical trial in mania. The trial lasted 14 days. Twenty-three patients who fulfilled Feighner's criteria for mania entered the trial (one patient entering on two separate occasions). Both drugs led to clinical improvement, with a significant effect being noted within 24 hours. According to one of the two rating scales used, initial improvement was greater with chlorpromazine, probably due to its greater sedative effect. By 7 days both drugs were equally effective. Sedative side effects were more frequent in patients on CPZ; extrapyramidal side effects were more frequent with PMZ. The finding that the relatively specific DA receptor blocking drug PMZ was as effective as CPZ in the treatment of mania is consistent with the view that hyperactivity of central DA pathways is involved in the pathogenesis of this condition.

Adult↗
PubMed1981

Relative speed of onset of the antidepressant effect of maprotiline.

In a double-blind clinical trial conducted in general practice, maprotiline was compared with amitriptyline. Thirty-three of 40 patients completed the trial, 19 on maprotiline and 14 on amitriptyline. The Hamilton Depression Rating Scale was administered on days, 0, 7, 14, and 21, and a global rating scale of improvement was administered on day 21. Although there were significant reductions in the Hamilton scores by day 21 in both groups, with no significant difference between the compounds, maprotiline produced significantly greater improvement by day 7 than did amitriptyline. A review of published double-blind clinical amitriptyline or imipramine for treatment of depression supports our finding that maprotiline has a faster onset of action than the standard tricyclic antidepressants.

Amitriptyline↗
PubMed1980

The effect of small and moderate doses of d-amphetamine on hunger, mood, and arousal in man.

In rats, low doses of d-amphetamine (d-amp) increase rather than decrease food intake. A double-blind study was carried out in nine healthy female subjects to compare the effects of a low (1 mg) and a moderate (10 mg) dose of d-amp and placebo on hunger, mood and arousal. Each subject participated in three experimental sessions, 1 week apart, when they received either 1 mg d-amp, 10 mg d-amp or placebo, according to a random double-blind design. Visual analogue rating scales for hunger, mood and arousal were completed prior to drug administration and at 30-min intervals for 4 h. A questionnaire relating to sleep pattern and side effects was completed the morning after each experimental session. d-Amp (10 mg) produced a significant reduction in hunger ratings as compared with placebo at 2 h and 2.5 h after administration, while 1 mg d-amp had no significant effect on hunger. Mood and arousal were only slightly elevated by 10 mg d-amp, and not at all by 1 mg.

Adult↗