Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The partial agonist at benzodiazepine receptors, Ro 19-8022, has been characterized as a putative anxiolytic drug with an improved side effect profile. This orally active compound is a representative of a quinolizinone structure class and shows potent anticonflict activity in mice and rats. It protects rodents from convulsions induced by pentylenetetrazol, N-methyl-D-aspartic acid and maximal electroshock, as well as against audiogenic seizures, with an efficacy comparable to that of the full agonist alprazolam. No appreciable sedative or motor-impairing effects could be detected up to a very high dose (100 mg/kg) in the horizontal wire test or the rotarod performance test in mice and rats and in spontaneous behavior in monkeys. Consistent with its characterization as a partial agonist, Ro 19-8022 antagonized the motor impairment induced by the full agonists diazepam or meclonazepam measured in horizontal wire and rotarod tests in rodents, and reduced flunitrazepam-induced effects in squirrel monkeys, with an efficacy comparable to that of the benzodiazepine receptor antagonist flumazenil. After subchronic administration of Ro 19-8022 to mice, antagonist-precipitated withdrawal syndrome was dramatically weaker than after alprazolam treatment, which is indicative of a lower physical dependence liability of Ro 19-8022. Pharmacodynamic effects recorded in convulsion and reversal of motor impairment tests after i.v. administration suggest a long duration of action of this compound. Taken together, such preclinical data suggest that benzodiazepine receptor partial agonists with a neurological and behavioral profile such as that of Ro 19-8022 may offer an innovative therapeutic approach to the treatment of anxiety disorders.
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PMID:Ro 19-8022, a nonbenzodiazepine partial agonist at benzodiazepine receptors: neuropharmacological profile of a potential anxiolytic. 135 50

Although reliable biological markers of dysfunctional childhood anxiety disorders are lacking, such disorders can be recognized by their symptoms. In separation anxiety and avoidance disorders, anxiety is limited to certain settings; in overanxious disorder, anxiety is generalized. Treatment for childhood anxiety disorders has included behavioral and pharmacologic intervention alone or in combination, but evidence of the efficacy of medical treatment is sparse. Some antidepressants and benzodiazepines have undergone limited studies. Clonazepam has been chosen for further study because in adults it reduced panic attacks and produced few serious side effects. In extensive studies of clonazepam for childhood seizure disorders, side effects were reported, but later reports indicate that many side effects were due to rapid induction and large doses. Transient drowsiness, lethargy, irritability, or excitability have been reported in various epilepsy studies. Clonazepam's minimal potential for drug interactions is another feature recommending it for extended trials in childhood anxiety disorders, and such a double-blind crossover study is underway.
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PMID:High anxiety in children. 218 21

Alcohol has widespread effects on the gamma-aminobutyric acid (GABA) system in the brain. This system in the brain is also postulated to have a role in anxiety, and alcoholics have been reported to have more anxiety disorders. Therefore, the authors undertook a study to compare CSF levels of GABA in abstinent alcoholic patients and normal control subjects. There was no significant difference between groups in CSF levels of GABA. Also, there was no significant difference in GABA level between alcoholic patients with histories of withdrawal seizures and those without such a history.
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PMID:CSF gamma-aminobutyric acid in alcoholics and control subjects. 239 95

Patients with alcohol dependence commonly experience symptoms of anxiety, depression, and insomnia. It is essential that clinicians recognize and treat anxiety disorders in alcoholic patients. Panic attacks with and without agoraphobia are especially prevalent among alcoholics and their families. Treatments of choice for panic disorder are the monoamine oxidase inhibitors, as well as tricyclic antidepressants and the benzodiazepine alprazolam. Benzodiazepines seem to be effective in controlling two pathophysiologic characteristics of alcohol withdrawal--noradrenergic and hypothalamic-pituitary-adrenocortical overactivity. They also can be used to prevent and treat withdrawal seizures and delirium tremens. They are not indicated for the treatment of alcohol dependence per se.
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PMID:Anxiety and alcoholism. 268 Nov 71

The authors followed up 107 patients with panic disorder or agoraphobia with panic attacks who had been placed on a regimen of tricyclic antidepressant treatment 1 to 4 years earlier. Sixty-three percent reported at least moderate improvement during treatment; however, side effects were often difficult to tolerate, and 35% discontinued tricyclic treatment on this account. Overstimulation, which occurred in 20%, was the most frequent reason for early termination, and weight gain, which occurred in 34%, was the most common reason for stopping the drug later on. Seizures occurred in 2 patients. Even though they were encouraged to discontinue drug use, most of the patients who had responded were still taking their drugs at follow-up. More than half of those who had responded before stopping drug treatment subsequently relapsed. The findings highlight problems with safety, side effects, and patient acceptance resulting from the use of tricyclic antidepressants in patients with anxiety disorders.
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PMID:Problems with tricyclic antidepressant use in patients with panic disorder or agoraphobia: results of a naturalistic follow-up study. 271 39

Anxiety has historically been treated by agents with a sedative component to their action. In the last decade or so it has been determined that gamma-aminobutyric acid (GABA) receptors may mediate the anxiolytic actions of the benzodiazepines, propanediol carbamates, barbiturates, and ethanol. However, inasmuch as these drugs have additional pharmacological properties (sedation, muscle relaxation, seizure control), the search for an anxioselective drug was continued. Buspirone appears to be such a drug. Clinical studies have clearly demonstrated the efficacy of buspirone in the treatment of generalized anxiety disorder without the ancillary pharmacology of earlier anxiolytics. Buspirone does not act on the GABA receptor. Rather, its most salient interaction with neurotransmitter receptors occurs at the 5-HT1A serotonin receptor. This action is supported by studies focused on receptor binding, anatomical localization, biochemistry, neurophysiology, and animal behavior. The recognition that action at 5-HT1A receptors may be a viable approach to the pharmacotherapy of anxiety is evidenced by the number of other agents of this class under development by a number of pharmaceutical companies.
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PMID:Buspirone, a new approach to the treatment of anxiety. 283 52

To investigate whether surgical treatment of refractory epilepsy is associated with increased risk for serious psychopathology, 25 treated patients were compared with 25 current candidates for surgery matched on demographic and neuroepileptic characteristics. Diagnoses were made by the National Institute of Mental Health Diagnostic Interview Schedule. No differences between groups in lifetime or point prevalence rates were significant. The rate of psychosis in the postoperative group (8%) approximated the lower estimates in previous studies. Thus, surgical treatment of seizures did not increase the risk for psychopathology. However, patients with temporal lobe electroencephalogram foci or tumor as the epileptogenic lesion were more likely to have serious disorders than other patients. Also, anxiety disorders were more prevalent in our patient groups than in the general population.
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PMID:Prevalence of psychologic disorders after surgical treatment of seizures. 319 90

Phenytoin has a wide range of pharmacologic effects other than its anticonvulsant activity. It has been the subject of more than 8,000 published papers, which include clinical reports of its usefulness in approximately 100 diseases and symptoms. In the United States the only indications for use in the official labeling for phenytoin are various types of seizures. An advisory committee of the Food and Drug Administration recently recommended the addition of certain cardiac arrhythmias to the labeling. To determine whether other uses should be added to the labeling and whether additional clinical trials should be encouraged, an in-depth review of the published literature was undertaken. This review revealed that, on the basis of controlled studies, phenytoin is probably useful in the continuous muscle fiber activity syndrome, myotonic muscular dystrophy, and myotonia congenita. In addition, phenytoin appears to be potentially useful in recessive dystrophic epidermolysis bullosa, intermittent explosive disorder, anxiety disorder in which anger and irritability are prominent features, and, topically, in burns and refractory skin ulcers. Additional clinical studies are needed before definitive conclusions can be drawn. Clinical trials of phenytoin in most of these disorders are ongoing or are contemplated. Any labeling changes will await results of the studies. Based on phenytoin's pharmacologic effects in animals, controlled trials of the drug appear to be warranted in cerebral ischemia and stroke, spinal cord injury, angina pectoris, and fractures in which the rate of healing is poor.
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PMID:Phenytoin revisited. 638 10

In a double-blind study the authors compared severity of psychopathology and personality organization in three groups of patients: those with organic (neurogenic) seizures alone (N = 11), those who exhibited both neurogenic and psychogenic ("hysterical") seizures (N = 13), and those with pure psychogenic ("hysterical") seizures (N = 13). Patients with neurogenic seizures were found to have alcoholism, anxiety disorder, and minor affective disorder. Patients with mixed and psychogenic seizures had more severe psychopathology, including major affective disorders and major character pathology. Patients with mixed and psychogenic seizures also had a markedly higher incidence of suicide attempts and past history of psychiatric treatment.
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PMID:Are hysterical seizures more than hysteria? A research diagnostic criteria, DMS-III, and psychometric analysis. 709 12

Panic disorder (PD) is a common psychiatric illness, which has many complications such as major depression, increased suicide risk, agoraphobic avoidance behaviour, alcohol abuse and dependence. A number of studies have now documented increased rates of anxiety disorders among alcoholics and of alcoholism among patients presenting with anxiety disorders. In general, it appears that PD is more prevalent in alcoholics than would be expected on the basis of general population rates. Alcohol withdrawal is clearly associated with severe anxiety symptoms. It is suggested that repeated withdrawal episodes may trigger panic through a kindling process by causing subconvulsive stimuli with increasing amounts of electrical excitability or even spontaneous seizures. Serotonergic medications are effective in treating PD and depression. They also diminish interest in drinking in ethanol-dependent patients. Serotonergic agents can also affect conditioning and learning as well as behavioral control and self-administration. The treatment of panic patients with depressive and alcohol problems usually requires long-term treatment.
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PMID:Alcohol and depression in panic disorder. 791 95


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