Advances in neurology
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Angelman syndrome is an inherited disorder that includes severe mental retardation and epilepsy. Patients have no speech, puppet-like gait with jerky movements, hyperactivity, disturbed sleep, bouts of inappropriate laughter, a pronounced jaw, and widely spaced teeth. The syndrome results from deletion or mutation within maternal chromosome 15q11-q13. ⋯ The GABRB3 gene, which codes for the beta 3 subunit, is deleted in most persons with Angelman syndrome. The absence of this gene in mice causes craniofacial abnormalities and neurologic impairment with seizures. The exact role of UBE3A and GABRB3 in the syndrome and their imprinting status are under investigation.
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Advances in neurology · Jan 1998
ReviewAssessing pharmacokinetic and pharmacodynamic interactions in clinical trials of antiepileptic drugs.
An understanding of the pharmacokinetic and pharmacodynamic properties of a drug is a basic requirement for its clinical use. The investigations of these properties and their timing are fairly clearly defined in the drug development process. Without fundamental knowledge of the pharmacokinetics and pharmacodynamics of a drug, a physician could not use it appropriately, nor would a regulatory agency be likely to approve its use. ⋯ Moreover, pharmacodynamic interactions, as opposed to pharmacokinetic interactions, are probably unidirectional and lead only to increased effects. Although it would be preferable to have this knowledge, an antiepileptic drug can be used effectively without it; over time, the information about pharmacodynamics will be inferred. Thus, conducting pharmacokinetic interaction studies with antiepileptic drugs early in their development as part of phase I is essential, whereas obtaining pharmacodynamic interaction information can be deferred.