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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kinetics and mechanism of action of benzodiazepines are at the base of their proper use in clinical management of anxiety, tension, panics, and insomnia. These important agents have specific receptors within the complex GABA-ergic system: according to the most recent studies, GABAA receptors are more important than GABAB receptors. The author illustrates the management of anxiety states, as well as the treatment of anxiety in children, in old people and of panic attacks. Since the use of benzodiazepines has become excessive, the risk of dependence is discussed as well as possible alternatives (buspirone, antidepressants). Finally, the usefulness of anxiolytic drug treatment is stressed which is one of the pivots of psychopharmacology and the study of the GABA-ergic system.
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PMID:[The mechanism of action of benzodiazepine and its consequences for therapy]. 135 Feb 39

Zolpidem is a nonbenzodiazepine hypnotic agent belonging to a new class of psychotropic drugs the imidazopyridines which enhance the GABAA receptor function by interacting with a specific receptor population. Zolpidem binds selectively to the Omega-1 receptor subtype and from a pharmacological point of view differs from benzodiazepines (BZD) by producing a strong sedative and hypnotic profile which predominates over the anticonvulsivant and anxiolytic activity and moreover appears practically devoid of myorelaxant properties. From a pharmacodynamic point of view, these results suggest that zolpidem facilitates more selectively than BZD, GABAA function and produces a selective hypnotic effect. Though if the role played by receptors in tolerance and dependence has not been yet fully elucidated, it could be described as an adaptative process to sustained stimulation of GABA function. Animal data obtained with zolpidem differs substantially from that of the BZD and indicates that repeated zolpidem administration may not lead to phenomena of tolerance and withdrawal syndrome after abrupt drug discontinuation. In human following oral intake, zolpidem is very rapidly (Tmax: 30-40 min) absorbed. The clearance is essentially metabolic and less than 1% is recovered in urine. The apparent plasma half-life is of 2.0-2.5 hours in most adult subjects and metabolites are totally inactive. The hypnotic activity of zolpidem and its effects on sleep architecture have been assessed in polysomnographic studies: 11 studies in 579 healthy volunteers and 12 studies in 202 insomniac patients. From all the patient studies, it emerges clearly that zolpidem at the dose of 10 mg significantly decreases sleep onset latency, the number and the duration of nocturnal awakenings, and concomitantly increases total sleep time. Furthermore, at variance with what observed with reference benzodiazepine hypnotics, zolpidem does not alter patient sleep architecture: it increases only moderately stage 2, it increases, when reduced, stages 3 and 4 (slow wave sleep) and it does not decrease REM sleep. Clinical studies conducted on more than 4,000 insomniac patients have clearly shown that at the dose of 10-20 mg, zolpidem induces from the first night a definite hypnotic effect in all types of insomnia. In elderly subjects an initial dose of 5 mg should be considered. The possible presence of residual effects during the day following administration of zolpidem has been assessed in 535 healthy volunteers and in 133 insomniac patients according to a double blind (versus placebo and/or benzodiazepine) controlled design.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Contribution of zolpidem in the management of sleep disorders]. 136 57

We report a case of Stiff-Man syndrome according to Gordon, Januszko and Kaufman's criteria. Onset at age 76, association with insomnia and a rapid course leading to death within 2 years were the characteristic features. CSF data, electromyographic and immunological findings suggest abnormalities of catecholaminergic and GABA ergic systems, with release of segmental or suprasegmental inhibitory influence. The presence of antibodies against glutamic acid decarboxylase, considered a useful marker of this syndrome, raises the possibility of an autoimmune pathogenesis.
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PMID:[Stiff-Man syndrome with late onset]. 144 49

The side-effect profile of quinolone antibiotics in man includes CNS disturbances such as dizziness, insomnia and convulsions. Although it has been suggested that the proconvulsive liability of quinolones involves an interaction with GABA receptors in the central nervous system, no animal model has been described to evaluate or confirm the mechanism of this effect. The proconvulsive activity of the quinolone antibiotics, nalidixic (NAL) and oxolinic (OXO) acid were tested in male mice following oral doses of 10-100 mg/kg utilizing the convulsive stimuli pentylenetetrazole (PTZ), picrotoxin, strychnine or electroshock. While NAL and OXO did not alter the threshold for convulsions induced by PTZ, strychnine or picrotoxin, both agents lowered the threshold for electroshock-induced seizures. Furthermore, the proconvulsive actions of NAL and OXO were completely blocked by the excitatory amino acid receptor antagonists, MK-801 and 2-amino-4-phosphonobutyric acid (AP-4). These data indicate that the mechanism of convulsive liability of quinolone antibiotics does not involve GABA receptor interactions as previously thought, but appears to involve activation of excitatory amino acid (EAA) receptors, possibly located in the optic region of the central nervous system.
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PMID:The proconvulsive activity of quinolone antibiotics in an animal model. 189 4

Sleep disorders are becoming a major issue. Insomnia affects a substantial part of the population and may compromise individual quality of life. The principal existing hypnotic drugs, Barbiturates and Benzodiazepines are not safely. They have modes of action which results in the action of common mechanism: facilitating neurotransmission in GABAergic synapses. Stimulation of GABA receptors of the A type opens chloride ion channels which inhibits the ability of neurons to conduct nerve impulse. The clinical effects resulting which induce anticonvulsant, muscle relaxant, anxiolytic, sedative, hypnotic and amnesic effects are discussed.
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PMID:[Pharmacologic aspects of sleep disorders]. 248 27

In order to analyse the role of the anterior hypothalamus in the regulation of the sleep-waking cycle we made bilateral neuronal lesions at different levels of the anterior hypothalamus in cats, by means of microinjections of a cell-specific neurotoxin:ibotenic acid. These lesions resulted in severe insomnia in eight cats. This insomnia was characterized by a large decrease or even disappearance of paradoxical sleep and deep slow wave sleep and, to a lesser extent, by a decrease of light slow wave sleep, for 2-3 weeks. In the other five animals, we observed a large reduction of deep slow wave sleep (0-40% of control level), but a less intensive decrease of time spent in paradoxical sleep (50-75% of control level) and no marked effect on light slow wave sleep. During the first 3-6 postoperative days we also noticed hyperthermia in all cats; thereafter, the animals presented only a slight increase in brain temperature which did not appear to trigger the sleep impairment. Histological analysis of the different lesions revealed that the insomnia could be attributed to neuronal cell body destruction in the mediobasal part of the anterior hypothalamus covering; the medial preoptic area and a narrow portion of the lateral preoptic area as well as a restricted part of the anterior hypothalamic nucleus. In order to investigate the putative role of the posterior hypothalamic structures in the mechanism of insomnia after lesion of the mediobasal preoptic area neurons we injected an agonist of GABA into the ventrolateral part of the posterior hypothalamus to locally depress the neuronal activity. The bilateral intracerebral microinjection of muscimol (0.5-5 micrograms) induced a transient intensive hypersomnia (slow wave sleep and paradoxical sleep). These findings indicate that neuronal cell loss in the mediobasal preoptic area induced a long lasting insomnia. Thus, it may be hypothesized that the integrity of this structure is necessary for sleep appearance. Finally, our data are in keeping with an intrahypothalamic regulation of the sleep-waking cycle.
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PMID:Long-lasting insomnia induced by preoptic neuron lesions and its transient reversal by muscimol injection into the posterior hypothalamus in the cat. 260 39

In order to investigate a possible involvement of the GABA-ergic neurotransmission in the effects of arginine vasotocin (AVT) hormone on human sleep, we administered in 20 healthy prepubertal boys (aged 7-12 years), by an intra-nasal route, AVT (1 microgram) alone or 10 minutes after an intra-nasal dose of valproic acid (VA) (1, 10 and 50 micrograms). Whether the dose of 50 micrograms VA alone produced a quasi-total insomnia for all recording time (3h), the doses of 1 and 10 micrograms VA were without any apparent effect on sleep parameters. However, whatever be the dose of VA, it produced a total suppression of the hypnogenic effects of AVT. The results suggest not only a possible involvement of the GABA-ergic mechanisms in mediating the hypnogenic properties of AVT in man, but also that VA could be used in the treatment of excessive sleep syndromes, especially of narcolepsy.
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PMID:Vasotocin and sleep in prepubertal boys: its suppression by valproic acid. 282 19

The development of new antiepileptic drugs in recent years has enlarged the number of anticonvulsant compounds for the treatment of intractable focal epilepsies. The anticonvulsant potency of these drugs is usually compared by the number of patients who achieve a reduction in seizure frequency of more than 50%. Such an effect can be observed in approximately 20-30% of patients with pharmacoresistant focal epilepsies and is about the same with all the new compounds. In addition to the influence on focal seizures some of the novel anticonvulsant drugs exhibit efficacy in generalized seizures or in Lennox-Gastaut syndrome. In general there are fewer side effects in newly developed drugs than in standard anticonvulsants. However, in some cases characteristic side effects may occur: weight gain, depression or psychosis from vigabatrin; lamotrigine may provoke allergic rashes and felbamate may cause gastrointestinal side effects and sleeplessness. Apart from felbamate, there are no interactions with an antiepileptic comedication or they are of little importance. The development of the new anticonvulsants follows a rational design based on pathophysiological aspects: the main aim is to influence synaptic transmission, resulting in an increase in inhibitory and a decrease in excitatory transmitters. Thus, vigabatrin and tiagabine enhance the endogenous GABA amount, whereas felbamate and remacemide interact with the NMDA-receptor complex. Because it is not possible to draw sufficient conclusions from add-on studies in clinical testing it is necessary to establish new forms of trial design. Monotherapy designs are favored because they lack possible interactions with comedication and make the anticonvulsant efficacy of the compound better comparable to those of established anticonvulsants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Anticonvulsive drug therapy. Historical and current aspects]. 754 58

Benzodiazepine hypnotics and analogs promote the inhibitory neurotransmitter GABA in the brain. The individual substances of this class differ mainly with respect to their elimination half-life. They are all effective hypnotics, but exhibit a number of undesired effects. Hypnotics should be administered generally for the short-term treatment of insomnia, and they should be prescribed for a prolonged time period only exceptionally.
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PMID:[Pharmacotherapy of sleep disorders using benzodiazepine hypnotics and their analogs]. 779 69

Evidence is presented that the most widely used and effective drugs used in the treatment of anxiety and insomnia act by indirectly activating GABA-A receptors in limbic regions of the brain. Since the discovery of the benzodiazepines, different classes of benzodiazepine receptor ligands (such as the cyclopyrroliones and imidazopyridines) have been developed which alleviate anxiety and insomnia by activating different sites on the benzodiazepine-GABA receptor complex to those activated by the 'classical' benzodiazepines as exemplified by temazepam and diazepam. There is evidence that natural ligands also exist in the mammalian brain which can modulate the benzodiazepine-GABA receptor complex. This raises the possibility that insomnia and anxiety states may arise as a consequence of a deficit in the availability of endogenous ligands that act as agonists at these sites.
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PMID:Sleep disorders and anxiety: biochemical antecedents and pharmacological consequences. 779 54


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