Reference

Behavioural effects of the newer antiepileptic drugs: an update

Behavioural effects of the newer antiepileptic drugs: an update. Besag, Frank M. C. (Specialist Medical Department, Twinwoods Health Resource Centre, Bedford, Bedfordshire MK41 6AT, UK). Expert Opinion on Drug Safety, 3(1), 1-8 (English) 2004 Ashley Publications Ltd. CODEN: EODSA9.Chemicals with cas numbers 60142-96-3 and 84057-84-1 also play role. ISSN: 1474-0338. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. The neg. and pos. effects of the nine newer antiepileptic drugs that have received a product license in the UK or in the US are reviewed. The importance of avoiding misinterpretation of the data because of confounding factors such as alternative psychosis, the release phenomenon or drug interactions is emphasized. Vigabatrin has been assocd. with both psychosis and depression. Due to the concentric visual field defects that may occur with vigabatrin, its use is now limited, although it remains the drug of choice for infantile spasms. Lamotrigine seems to be largely assocd. with improvement rather than deterioration of mood and behavior. It may have a role in treating affective disorder. Gabapentin probably has relatively little effect on behavior but may exacerbate behavioral problems in some children with pre-existing difficulties. Topiramate may ppt. both psychosis and depression, but these are less likely to occur if the currently recommended lower starting doses, escalation rates and target doses are used. The data for tiagabine are limited, but there is no clear evidence for psychosis or depression being caused by this drug. Oxcarbazepine may be of value in treating mood disorder, but the information is very limited. There are few reports of behavioral disturbances with levetiracetam, but the data suggest that there is no significant increase in psychosis or depression. There are some reports of psychosis and other behavioral disturbances with felbamate, but the use of this drug is limited by the serious adverse effects of hepatotoxicity and aplastic anemia. There is some evidence for psychosis with zonisamide, but there is also a suggestion that this drug may be of benefit in treating psychiatric disorders. Careful individual assessment of each patient should enable the clinician to det. whether the medication or some other factor is responsible for any behavioral disturbance. .

Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine

Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine. Pisani, Antonio; Bonsi, Paola; Martella, Giuseppina; de Persis, Cristiano; Costa, Cinzia; Pisani, Francesco; Bernardi, Giorgio; Calabresi, Paolo (Clinica Neurologica, Dipartimento di Neuroscienze, Universita di Roma "Tor Vergata", Italy). Epilepsia, 45(7), 719-728 (English) 2004 Blackwell Publishing, Inc. CODEN: EPILAK. ISSN: 0013-9580. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Purpose: Alterations in neuronal calcium (Ca2+) homeostasis are believed to play an essential role in the generation and propagation of epileptiform events. Levetiracetam (LEV) and lamotrigine (LTG), novel antiepileptic drugs (AEDs), were tested on epileptiform events and the corresponding elevations in intracellular Ca2+ concn.Some commonly used reagents like 102767-28-2 and 84057-84-1 are used in this experiment. ([Ca2+]i) recorded from rat neocortical slices. Methods: Electrophysiol. recordings were performed from single pyramidal neurons from a slice prepn. Spontaneous epileptiform events consisting of long-lasting, repetitive paroxysmal depolarization shifts (PDSs) and interictal spike activity were induced by reducing the magnesium concn. from the soln. and by adding bicuculline and 4-aminopyridine. Simultaneously, microfluorimetric measurements of [Ca2+]i were performed. Optical imaging with Ca2+ indicators revealed a close correlation between Ca2+ transients and epileptiform events. Results: Both LEV and LTG were able to reduce both amplitude and duration of PDSs, as well as the concomitant elevation in [Ca2+]i, in a dose-dependent fashion. Whole-cell patch-clamp recordings from isolated neocortical neurons revealed that LEV significantly reduced N-, and partially P/Q-type high-voltage-activated (HVA) Ca2+ currents, whereas sodium currents were unaffected. Interestingly, the inhibitory effects of LEV were mimicked and occluded by LTG or by a combination of o-conotoxin GVIA and o-agatoxin IVA, selective blockers of N- and P/Q-type HVA channels, resp., suggesting a common site of action for these AEDs. Conclusions: These results demonstrate that large, transient elevations in neuronal [Ca2+]i correlate to epileptiform discharges. The antagonistic effects of LEV and LTG on [Ca2+]i overload might represent the basis for their anticonvulsant efficacy and could preserve neuronal viability. .