Weak blockade of AMPA receptor-mediated depolarisations in the rat cortical wedge by phenytoin but not lamotrigine or carbamazepine

European Journal of Pharmacology
I PhillipsD J Heal

Abstract

The effects of the anticonvulsants, lamotrigine, phenytoin and carbamazepine, were investigated on NMDA and non-NMDA receptor agonist-evoked responses and against spontaneous epileptiform discharges, in the in vitro rat cortical wedge. Lamotrigine weakly attenuated responses to (RS)-alpha-amino-3-hydroxy-5-methoxy-4-isoxazole propionic acid (AMPA) and quisqualate (IC50 values > 100 microM), but was without effect on responses to NMDA. Phenytoin weakly, but concentration-dependently, attenuated responses to AMPA and quisqualate, but much less potently attenuated responses to NMDA (IC50 values 163, 248 and > 300 microM, respectively). Carbamazepine (3-100 microM) significantly attenuated responses to NMDA and at 100 microM attenuated responses to AMPA and quisqualate. These effects were not concentration dependent, with the IC50 values > 100 microM. Lamotrigine and phenytoin weakly, but concentration-dependently, reduced the frequency (IC50 values 254 and > 300 microM, respectively) and amplitude (IC50 values 141 and > 300 microM, respectively) of spontaneous epileptiform discharges, whereas carbamazepine had no effect. The results show that the anticonvulsant effects of these antiepileptics are unlikely to involve antagonism of ...Continue Reading

References

Jan 1, 1991·Epilepsia·M J LeachM A Critchley
Dec 19, 1989·European Journal of Pharmacology·M J SheardownT Honoré
Feb 1, 1985·British Journal of Pharmacology·N L Harrison, M A Simmonds
Mar 21, 1994·European Journal of Pharmacology·L M BrownT J Teyler

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Citations

Sep 15, 2014·Neuroscience and Biobehavioral Reviews·Mehdi GhasemiAhmad Salehi
Nov 8, 2011·Epilepsy & Behavior : E&B·Mehdi Ghasemi, Steven C Schachter
May 24, 2011·Journal of Affective Disorders·Konstantinos N FountoulakisHagop Akiskal
Mar 1, 2012·European Journal of Pharmacology·Suzanne L HansenHenrik T Vestergaard
Oct 29, 2005·European Journal of Pharmacology·Brian P Kirby, Graham G Shaw

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