Lamotrigine.
Lamotrigine (LTG) is a novel antiepileptic drug (AED) with a spectrum of activity in animal models of epilepsy similar to that of phenytoin and carbamazepine. In some models it appears to have a broader spectrum and better tolerability than these agents, however. One mechanism of action of LTG is the marked inhibition of release of the excitatory neurotransmitters glutamate and aspartate under conditions of sustained repetitive firing. LTG appears to do this by blocking voltage-sensitive sodium channels and has no direct effect on N-methyl-D-aspartate (NMDA) receptors. In clinical trials as add-on therapy in medically refractory partial seizure patients, LTG has consistently produced a 50% reduction in seizure frequency in 25-34% of subjects. LTG is well tolerated, even in the add-on situation. In part, this appears to be related to positive behavioral effects. Desirable pharmacologic properties of LTG include low protein binding (55%), an absence of enzyme induction, and linear pharmacokinetics. The most significant adverse effect is rash, leading to a withdrawal rate of 2% of patient exposures in clinical trials.
Messenheimer
J A
JA
Department of Neurology, University of North Carolina School of Medicine, University of North Carolina at Chapel Hill 27599-7025, USA.
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D004347:Drug Interactions; D016903:Drug Monitoring; D004827:Epilepsy / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D000077213:Lamotrigine; D051379:Mice; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D016896:Treatment Outcome; D014227:Triazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000927:Anticonvulsants; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D014227:Triazines; D000077213:Lamotrigine