Carbamazepine and phenytoin, two of the most commonly prescribed antiepileptic drugs, have been proposed to share a similar mechanism of action by use-dependent inhibition of Na+ channels. The proposed similar mechanism of action, however, cannot explain the common clinical experiences that the two drugs are different; in some patients, one drug may be more effective than the other. This may occur even when optimal therapeutic concentrations are reached with both medications in plasma or the cerebrospinal fluid. In this study, we show that the action of the two drugs on Na+ channels are quantitatively very different. The affinity between inactivated Na+ channels and carbamazepine (apparent dissociation constant approximately 25 microM) is approximately 3 times lower than that of phenytoin, yet the binding rate constant of carbamazepine onto the inactivated Na+ channels is approximately 38,000 M(-1)/sec(-1), or approximately 5 times faster than that of phenytoin. It is speculated that carbamazepine may be more effective than phenytoin in treating seizures whose ictal depolarization shift is relatively short, whereas a better response to phenytoin may imply abnormal discharges characterized by more prolonged depolarization.

1 Lamotrigine (LTG), a new antiepileptic drug, requires long depolarizations to inhibit Na + currents. This suggests either slow binding of LTG to the fast inactivated state or selective binding of LTG to the slow inactivated state of Na + channels. To di erentiate between these possibilities and to characterize further the action of LTG, we studied the a nity and kinetics of LTG binding to the Na + channels in acutely dissociated hippocampal neurones of the rat. 2 LTG inhibited more Na + currents at more depolarized holding potentials. The inhibitory e ect at various holding potentials could be described by one-to-one binding curves, which yielded an apparent dissociation constant of *7 mM for LTG binding to the inactivated channels (K I ), and a dissociation constant more than 200 times larger for LTG binding to the resting channels. A similar value of K I (*9 mM) was also derived from the LTG concentration-dependent shift of the inactivation curve. 3 The recovery of LTG-bound inactivated Na + channels was faster than the recovery of normal (drugfree) slow inactivated channels. Moreover, the binding kinetics of LTG onto the inactivated channels were faster than the development of the slow inactivated state, and were linearly correlated with LTG concentrations, with a binding rate constant of *10,000 M 71 s 71 . These ®ndings suggest that LTG chie¯y binds to the fast inactivated state rather than the slow inactivated state. 4 We conclude that LTG, in therapeutic concentrations and at relatively depolarized membrane potentials, may potently inhibit Na + currents by slow binding to the fast inactivated state of Na + channels. Like phenytoin, the slow binding rates may explain why LTG e ectively inhibits seizure discharges, yet spares most normal neuronal activities.

Family-centered care facilitated short-term medical and neurobehavioral outcomes in VLBW preterm infants in Taiwan; the effects were likely achieved through parental adherence to interventions. The designated strategies may be considered in a future launch of family-centered care in Taiwan.

Knowledge of the determinants of QOL could serve as a guide in a holistic approach to evaluation and intervention and help plan interventions targeted at these determinants to improve the QOL of caregivers of children with CP. Implications for Rehabilitation Caregivers of children with CP had lower QOL, except the environment QOL. The QOL determinants of caregivers of children with CP are multidimensional, including child characteristics, caregiver characteristics, and environmental factors. In addition to child characteristics of severity of fine motor impairments and emotional and behavioural problems, caregiver characteristics of general mental health, parenting stress, and coping patterns, and environmental factors of family life impacts, and school setting demonstrated important relationships with caregiver QOL.

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