4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies. 4.2 Posology and method of administration Oral administration. Posology The dose is one tablet of 35mg of trimetazidine twice daily during meals. Special populations Renal impairment In patients with moderate renal impairment (creatinine clearance [30-60] ml/min) (see sections 4.4 and 5.2), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Elderly Elderly patients may have increased trimetazidine exposure due to age-related decrease in renal function (see section 5.2). In patients with moderate renal impairment (creatinine clearance [30-60] ml/min), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Dose titration in elderly patients should be exercised with caution (see section 4.4). Health Products Regulatory Authority

Summary of product characteristics

LaBar and Cabeza review the powerful effects of emotion on memory. These influences are mediated by the amygdala and its interactions with medial temporal and prefrontal regions, and affect memory from the encoding and consolidation stages through to long-term retrieval.

/pdf/cognitive-neuroscience-of-emotional-memory-4ysnwazj1n.pdf

Cognitive neuroscience of emotional memory

Antiepileptic drugs (AEDs) provide satisfactory control of seizures for most patients with epilepsy. The drugs have the remarkable ability to protect against seizures while permitting normal functioning of the nervous system. AEDs act on diverse molecular targets to selectively modify the excitability of neurons so that seizure-related firing is blocked without disturbing non-epileptic activity. This occurs largely through effects on voltage-gated sodium and calcium channels, or by promoting inhibition mediated by GABAA (γ-aminobutyric acid, type A) receptors. The subtle biophysical modifications in channel behaviour that are induced by AEDs are often functionally opposite to defects in channel properties that are caused by mutations associated with epilepsy in humans.

/pdf/the-neurobiology-of-antiepileptic-drugs-1r9ke7ur3e.pdf

The neurobiology of antiepileptic drugs.

Synaptic plasticity is a key component of the learning machinery in the brain. It is vital that such plasticity be tightly regulated so that it occurs to the proper extent at the proper time. Activity-dependent mechanisms that have been collectively termed metaplasticity have evolved to help implement these essential computational constraints. Various intercellular signalling molecules can trigger lasting changes in the ability of synapses to express plasticity; their mechanisms of action are reviewed here, along with a consideration of how metaplasticity might affect learning and clinical conditions.

Metaplasticity : tuning synapses and networks for plasticity

The neurobiology and control of anxious states

Lamotrigine (LAG) is a new anticonvulsant drug for the treatment of partial and secondarily generalized seizures. The present study was aimed at elucidating the possible involvement of Ca2+ channels in the action of LAG using whole-cell patch clamp recordings in acutely dissociated amygdalar neurones. Whole-cell Ca2+ currents (ICa) were elicited by 200 ms step commands from -70 mV to -10 mV. Application of LAG reduced the ICa by an average of 40.3 +/- 3.2%. The inhibition of ICa by LAG was markedly reduced or eliminated in the presence of the N-type Ca2+ channel blocker omega-conotoxin-GVIA (1 microM). These results suggest that LAG may exert its anticonvulsant effect through inhibition of presynaptic N-type Ca2+ channels, thereby reducing glutamate release.

Inhibition of N-type calcium currents by lamotrigine in rat amygdalar neurones.

Valproic acid suppresses the synaptic response mediated by the NMDA receptors in rat amygdalar slices.

Summary: Purpose: A prospective population-based case-control study was performed to ascertain whether febrile convulsion (FC) in early childhood is associated with neurocognitive attention deficits in school age.



Methods: A total of 103 children, confirmed to have FC by age 3 years from a population survey of 4,340 live-birth new-borns in Tainan City, Taiwan, was followed up until at least age 6 years. An achievement test, behavioral ratings, and computerized neurocognitive battery assessing various subcomponents of attention were given to 87 FC children (FC group) and 87 randomly selected population-matched control (CC group).



Results: Compared with the CC group, the FC group did not have scholastic performance or behavioral outcome disadvantage. Overall FC group performance was distinguished by significantly higher scores in the achievement test and fewer missing errors (p <0.005) and commission errors (p <0.05), less variability in reaction time (p <0.005), and a nonsignificant trend of impulsivity. Attention performance of the FC and CC groups were comparable. Within the FC group, age at onset, complex FC, recurrence of FC, development of unprovoked seizures, or prior use of phenobarbital had no adverse effects on neurocognitive attention outcome.



Conclusions: This population study suggests that FC in early childhood does not have adverse effects on behavior, scholastic performance, and neurocognitive attention. On the contrary, the FC group demonstrated significantly better control of distractibility and attention at school age.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1157.2000.tb00182.x

Neurocognitive attention and behavior outcome of school-age children with a history of febrile convulsions: a population study.

Summary: Purpose: To identify risk factors for a first febrile convulsion among 3-year-old children by a matched case-control population study.



Methods: All 11,714 neonatal survivors born in Tainan City between October 1989 and September 1991 were enrolled. At age 3, 10,460 children were available for telephone survey for febrile convulsions, and were confirmed by home visit interviews. Those without history of seizure were randomly matched to each febrile convulsion case by age, gender, and residence district.



Results: Two hundred fifty six children had febrile convulsions, and 218 of them and their matched controls were available for analysis. The febrile convulsion cases had significantly more febrile episodes (four or more) per year (33.0 vs. 22.5%; p = 0.021), and cases had a higher percentage of developmental delay (3.7 vs. 0.4%; p = 0.046) and a higher percentage of febrile convulsions in their siblings (12 vs. 0.4%; p = 0.011) than controls. The other sociodemographic, environmental, and biologic variables showed no differences between cases and controls. Step-wise logistic regression showed a highly significant independent association between febrile convulsions and history of febrile convulsions in the siblings, and a moderate one between febrile convulsions and the number of febrile episodes per year.



Conclusions: The presence of febrile convulsions in the siblings and the number of fever episodes per year were the independent and significant predictors of febrile convulsion for an individual case in our population-based sample.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1157.1999.tb00769.x

Jing Jane Tsai

Papers

Inhibition of N-type calcium currents by lamotrigine in rat amygdalar neurones.

Valproic acid suppresses the synaptic response mediated by the NMDA receptors in rat amygdalar slices.

Neurocognitive attention and behavior outcome of school-age children with a history of febrile convulsions: a population study.

Risk factors for a first febrile convulsion in children: a population study in southern Taiwan.

Melatonin potentiates the GABAA receptor-mediated current in cultured chick spinal cord neurons