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)

A synthetic procedure for the preparation of imidazolidinediones by the base-catalyzed cyclization of propargylureas is described. This method appears to be the most versatile way of obtaining these compounds containing tertiary groups substituted on ring-nitrogen number 3. One of these derivatives, 3-tert-butyl-5,5-dimethyl-2,4-imidazolidinedione (1a), has shown a moderate level of subcutaneous metrazole seizure threshold activity (scMet indicates potential for control of petit mal epileptic seizures) in control screens on mice, as determined by the National Institute of Neurological and Communicative Disorders and Stroke.
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PMID:Synthesis of imidazolidinediones and oxazolidinediones from cyclization of propargylureas and propargyl carbamates. 45 26

A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate++ + (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of greater than 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed.
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PMID:Synthesis and anticonvulsant activity of enaminones. 149 12

Severe myoclonic epilepsy of infancy (SMEI) is a newly recognized epileptic syndrome. It is characterized by multiple febrile seizures, often prolonged, subsequent development of uncontrollable mixed-myoclonic seizures, and, eventually, psychomotor retardation. Drugs for myoclonic epilepsy--valproate (VPA), the suximides, and the benzodiazepines--have been shown to be useful in SMEI. Among children with seizures in the National Institute of Neurological and Communicative Disorders and Stroke Collaborative Perinatal Project (NCPP), one individual with SMEI was identified. This finding from the NCPP suggests that the incidence of SMEI is approximately 1 in 40,000 children. Such an incidence is supported by observations at the Texas Tech University Health Sciences Center.
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PMID:Epidemiology of severe myoclonic epilepsy of infancy. 169 45

Previous results of anticonvulsant activity in several imidooxy carboxylates related to (aminooxy)acetic acid in young chicks, prompted an in-depth reinvestigation of these analogues in mice. A series of 22 succinimidooxy, phthalimidooxy, and naphthalimidooxy carboxylates were synthesized and evaluated for anticonvulsant activity by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Methyl (succinimidooxy)acetate (2d), ethyl (succinimidooxy)acetate (2e), methyl (phthalimidooxy)acetate (3d), ethyl (phthalimidooxy)acetate (3e), and ethyl 2-(phthalimidooxy)propionate (3g), which were initially found to be active as anticonvulsants in young chicks were uniformly inactive in the Phase I seizure tests involving maximal electroshock (MES), pentylenetetrazol (scMet), or neurologic toxicity toxicity (Tox). Several newer analogues, ethyl (succinimidooxy)formate (2c) and methyl 3-(phthalimidooxy)-2-methylacrylate (4h) were found to be active in the scMet (3a) or both (4h) evaluations. Most interesting was the anticonvulsant results of N-(benzyloxy)-2-azaspiro[4,4] nonane-1,3-dione (5b), which displayed anti-MES activity and a protective index (TD50/ED50) of greater than 4.5.
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PMID:Synthesis and anticonvulsant activity of imidooxy derivatives. 199 41

We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one nonfebrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.
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PMID:Predisposing and causative factors in childhood epilepsy. 362 20

The Epilepsy Branch of the National Institute of Neurological and Communicative Disorders and Stroke has responded to the need for new, more effective, and less toxic antiepileptic drugs by cooperating with pharmaceutical companies in key areas of development. The ADD Program screens large numbers of compounds for anticonvulsant activity in appropriate animal models and sponsors clinical trials of promising new drugs for the treatment of epilepsy. The use of investigative techniques developed since the late 1960s allows documentation of seizure type and seizure frequency for maximal objectivity of clinical trial data.
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PMID:Antiepileptic drug development program. 635 Nov 1

This discussion addresses the questions of the parinatal, neonatal, and infant health and development of children born to adolescent mothers as related to other biologic and social factors. Medical and legislative plans for adolescent mothers and their infants must be based on assessment of both mortality and morbidity of the infants born to adolescent mothers. Focus here is on neonatal data on 55,711 pregnancies collected by the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke; neonatal data from the University of Kansas Medical Center covering 4000 pregnancies, 770 of which were gestations in teenage mothers; and obstetric, perinatal, and neonatal data concerning 6087 pregnancies in 1976, 1977, and 1978 at the Regional Perinatal Center at the University of Rochester. Ample evidence suggests a strong association between maternal age and birth weight. In particular, Hardy and Mellits found a higher frequency of low birth weight infants born to young black women. Interactions with other variables, including parity, clearly illustrate that firstborn infants are lighter than subsequent infants up to a maternal age of 35. Hoffman et al. have demonstrated that American women 18 years and under show a tendency to have infants of shorter gestational age than women 19-24 years of age. Cigarette smoking, alcohol and drug abuse, prolonged rupture of membranes, seizure disorders, and gonorrhea were significantly more frequently diagnosed in teenage mothers. The studies showed that behavioral and medical complications in the mothers were more powerful determinants of infants born with weight of less than 2500 gm than maternal age alone. In sum, when maternal and fetal growth retarding factors are taken into account among mothers of specific age categories, no biologic disadvantage appears unique to adolescent mothers. Findings fail to support the often expressed view that the mother's biologic immaturity is the main factor responsible for excessive fetal and neonatal deaths in infants born to very young mothers. Proportionately more infants born to adolescent mothers required admission to the intensive care or special care nurseries at the University of Rochester hospital than did infants born to mothers in their 20s (15.77% versus 13.9%). The data suggest that the mothering skills and child rearing practices of adolescent childbearing women have yet to be evaluated adequately.
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PMID:The infants of adolescent mothers. 736 May 10

Valproic acid, an antiepileptic drug, is extensively metabolized in humans. Two putative metabolites, 2-n-propyl-3-aminopentanoic acid (3-aminovalproic acid, 3-amino-VPA; 2a) and 2-n-propyl-4-aminopentanoic acid (4-amino-valproic acid, 4-amino-VPA; 4a), which may result from the transamination of the respective keto acids 1a and 3a may explain the unusual extended seizure protection elicited by valproic acid. The title compounds were synthesized as their diasteriomeric ethyl esters 2b and 4b and submitted for anticonvulsant evaluation by the Antiepileptic Drug Development Program of the National Institute of Neurological and Communicative Disorders and Stroke. The results verified our hypothesis, as 4b was active in the subcutaneous pentylenetetrazol (scMet) evaluation at 30 mg/kg. Both compounds were highly toxic at 300 mg/kg.
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PMID:Synthesis and evaluation of amino analogues of valproic acid. 805 18

Ten affected individuals are described from a kindred with autosomal dominant familial Alzheimer's disease in which a mutation in the amyloid precursor protein gene results in a valine to glycine substitution at amyloid precursor protein 717 which co-segregates with the disease. The mean age at onset of symptoms was 52 years with a range from 40 years to 67 years. The median duration of the disease was 11 years, with a range of 7-16 years. All individuals fulfilled the National Institute for Neurological and Communicative Disorders and Stroke criteria for probable Alzheimer's disease. A homogeneous clinical and neuropsychological pattern was evident within the family. Myoclonic jerks, seizures, depression and a lack of insight were common features. Positron emission tomography demonstrated biparietal bitemporal hypometabolism in the one affected individual who was studied. The diagnosis was confirmed histopathologically in one individual.
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PMID:Familial Alzheimer's disease. A pedigree with a mis-sense mutation in the amyloid precursor protein gene (amyloid precursor protein 717 valine-->glycine). 846 68

A series of 25 children, 13 females and 12 males, who had an acquired communication disorder together with epilepsy, but did not fulfil the strict criteria of the Landau-Kleffner syndrome, was studied. All children had a clinical neurological evaluation, speech and language assessment, an awake and sleep EEG, cranial MRI, SPET scan, and audiometry. Clinical seizures were most often polymorphic in type (17 of 25). Atypical absences were the commonest individual seizure type occurring in 15 cases. All patients had an unequivocal epileptiform EEG. Normal sleep phenomena were only observed in 10 cases, enhancement of epileptiform activity in sleep was seen in 16. Cranial MRI was abnormal in six and normal in 19 cases. The SPET scans were abnormal in 22 of 25 children. The language deficits were classified neurologically as receptive aphasia, 24 of 25; expressive aphasia, 20 of 25; nominal aphasia, eight of 25; articulatory dyspraxia, 10 of 25; and auditory agnosia, nine of 25. It is hypothesized that the loss of communication skills is due to an encephalopathy secondary to the persistent epileptic discharge and manifests as a hypometabolic area on the SPET scan.
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PMID:Epileptic aphasia: a consequence of regional hypometabolic encephalopathy? 974 2


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