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ABSTRACT: Benzodiazepines were first discovered in the mid 1950s when Sternbach, a medicinal chemist in New Jersey, began synthesising
compounds with a bicyclic nucleus benzo-1, 4-diazepine structure. One compound, chlordiazepoxide (Fig. 1), exhibited sedative,
anticonvulsant and muscle relaxant properties, which were confirmed by clinical studies and was launched as an anxiolytic
in 1960 under the trade name Librium. A second compound, diazepam (valium), which was more potent and had a broader spectrum
of activity than chlordiazepoxide [1], was introduced in 1963. Since then, numerous analogues of the benzodiazepine structure have been developed and introduced
into clinical practice.
07/2011: pages 1-11;
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ABSTRACT: To compare executive, memory and visuospatial functioning of DSM-IV anorexia nervosa (AN), bulimia nervosa (BN), and normal controls (NC).
A comparison of women involving: (i) 16 AN with body mass indices (BMI) < or = 17.5 kg/m(2); (ii) 12 AN with BMI > 18.5 kg/m(2) for at least 3 months; (iii) 13 BN; and (iv) 16 NC participants was performed with groups of similar age and intelligence. Groups were assessed with EDE-12, MADRS, HAMA, Cognitive Drug Research (CDR) battery, and Bechara tasks.
Significant impairments in CDR Power of Attention were present in underweight AN and BN participants. CDR Morse Tapping was significantly impaired in all clinical groups. The BN and weight-recovered AN groups were significantly impaired on CDR immediate word recall. The BN group alone was significantly impaired on CDR delayed word recall.
Attentional impairment is similar in AN and BN. Impaired motor tasks in AN persist after "weight-recovery" and are similar to impairments in BN. BN may be discriminated from AN on word recall.
International Journal of Eating Disorders 11/2007; 40(7):613-21. · 2.95 Impact Factor
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ABSTRACT: The super-sensitivity of the neurohormone melatonin to light in patients with bipolar disorder provides evidence of the circadian nature of the disorder. This response has been proposed as an endophenotype for identifying people at risk of the disorder and guiding investigations of molecular genetic targets. However, before this response is used as an endophenotypic marker, the heritable nature of melatonin sensitivity in the normal population must be established. The aim of this study was to investigate the heritability of nocturnal melatonin secretion and sensitivity to light in monozygotic and dizygotic twins with no psychiatric history. This study investigated overall melatonin levels (between 2000 and 2400 h) and suppression by 500 lx of light (between 2400 and 0100 h) in 20 pairs of twins (nine monozygotic, 11 dizygotic). The results indicate that melatonin secretion is highly heritable with secretion in one twin being a significant predictor of secretion in their twin in both monozygotic and dizygotic pairs. In relation to light sensitivity, genetic loading appears to play a significant role with the greatest concordance between monozygotic twins, followed by dizygotic twins and finally low concordance in unrelated individuals. This provides additional support for the usefulness of melatonin sensitivity to light as a potential endophenotypic marker of bipolar affective disorder.
Psychoneuroendocrinology 09/2006; 31(7):867-75. · 5.81 Impact Factor
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ABSTRACT: Sensitivity of the pineal hormone melatonin to bright light at night has been posited as a putative marker of affective disorders. Research demonstrates melatonin supersensitivity to light in bipolar disorder, however the role that lithium carbonate plays in this response is unclear. This study assessed the effect of lithium on nocturnal melatonin secretion and sensitivity to light in healthy adults. Ten participants, tested on two nights, had blood samples drawn between 20:00 and 02:30 hours. On testing nights participants were exposed to 200 lux of light between 24:00 and 01:00 hours. Participants took 250 mg of lithium daily for 5 d between testing nights. The results indicated that lithium had a significant effect on sensitivity to light but not on overall melatonin synthesis. This finding has implications on the true magnitude of the melatonin light response in people with bipolar disorder and may elucidate possible mechanisms of action of lithium.
The International Journal of Neuropsychopharmacology 07/2005; 8(2):255-9. · 4.58 Impact Factor
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ABSTRACT: To assess the cognitive and psychomotor effects of single oral doses of valerian in healthy volunteers in comparison with a placebo and the hypnotic agent triazolam.
In a double-blind, placebo-controlled, four-way crossover study nine healthy subjects (5 males, 4 females) received in random order valerian 500 mg, valerian 1000 mg, triazolam 0.25 mg and placebo. Doses were separated by a wash-out period of at least 1 week. Subjects were tested before each dose and at 2, 4 and 8 h after the dose of each compound using the critical flicker fusion (CFF), choice reaction time (CRT), digit symbol substitution test (DSST), symbol search test (SST), digit span test (DST) and visual analogue scales of mood.
Repeated measures ANOVA was used to examine the changes in performance on tests over time and significant effects were further analysed using simple main effects analysis with least significant difference corrections. Statistically significant differences were only noted for the cognitive tests: SST (F(3, 8)=3.182, p<0.05) and DSST (F(3, 8)=9.688, p<0.005). In both cases the differences between groups were due to the effects of triazolam.
These data confirm that at recommended therapeutic doses, triazolam has detrimental effects on cognitive processes in healthy volunteers as found in previous studies. Valerian was without effect on either cognitive or psychomotor performance in healthy volunteers at the doses used in this study. Should the hypnotic activity of valerian be confirmed in randomized double-blind trials it may be a less troublesome alternative to benzodiazepines in the treatment of insomnia.
Human Psychopharmacology Clinical and Experimental 01/2004; 18(8):619-25. · 2.48 Impact Factor
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ABSTRACT: Depression is an incapacitating disorder with serious health and economic consequences. It has an estimated cost of more than
$ 43 billion annually in the US (Greenberg et al., 1993) and by the year 2020 it will be the second leading cause of disease burden behind ischaemic heart disease (The Global Burden of Disease and Injury Series, 1996). Despite extensive research, very little is known about the aetiology of depressive illness or the mechanism of action of
drugs used in its treatment. Although effective, there are a number of disadvantages to the use of antidepressants. Firstly,
there is a delay of 3-4 weeks before any therapeutic effects of these drugs are seen. This is a serious problem since there
is an increased incidence of suicide in depressed patients and a lifetime incidence of suicide of 15% has been reported from
follow-up studies (Smith and Weissman, 1992; Norman and Leonard, 1994). Secondly, antidepressants, particularly the early generation, are often associated with unpleasant side effects such as
dry mouth, blurred vision, urinary hesitancy, dizziness on standing, which reduce patient compliance. Improvements have been
made with newer antidepressants which are based on the same mechanism of action. Venlafaxine blocks the reuptake of noradrenaline
and serotonin but lacks the alpha 1, cholinergic and histaminergic receptor blocking properties of the TCA’s, while nefazodone,
the 5-HT2 receptor antagonist, has less side-effects than the SSRI’s.
12/2000: pages 47-61;
