Excitatory amino acid transmitters in epilepsy.
For the majority of human epilepsy syndromes, the molecular and cellular basis for the epileptic activity remains largely conjectural. The principal hypotheses currently concern: defects in membrane ionic conductances or transport mechanisms; defects in gamma-aminobutyric acid (GABA)-mediated inhibitory processes; and enhanced or abnormal excitatory synaptic action. Substantial evidence exists in humans and animals for acquired abnormalities in excitatory amino acid neurotransmission that may participate in the abnormal patterns of neuronal discharge, and this could provide the morphological basis for a recurrent excitatory pathway sustaining seizure discharges in temporal lobe epilepsy. In practice, two approaches appear significant in the suppression of seizures. One is to act postsynaptically on receptors to decrease the excitation induced by glutamate, and the other is to decrease synaptic release of glutamate and aspartate. Agents acting upon adenosine or GABAB receptors decrease glutamate release in vitro but do not have significant anticonvulsant activity, probably because of their predominant actions at other sites. Lamotrigine blocks stimulated release of glutamate and shows anticonvulsant activity in a wide range of animal models.
Meldrum
B S
BS
Institute of Psychiatry, London, England.
D000927:Anticonvulsants / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000378:metabolism / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D005971:Glutamates / Q000378:metabolism* / Q000502:physiology; D018698:Glutamic Acid; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D000077213:Lamotrigine; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000502:physiology; D014227:Triazines / Q000627:therapeutic use*
D000927:Anticonvulsants; D005971:Glutamates; D007473:Ion Channels; D018377:Neurotransmitter Agents; D014227:Triazines; D001224:Aspartic Acid; D018698:Glutamic Acid; D000077213:Lamotrigine