THE action of TMB-8 [8-N,N-diethylamino)octy-3,4,5-trimethoxybenzoate]
on glutamate (Glu)- and 55 mM KCl (K+)-induced increases in intracell
ular free calcium levels ([Ca2+](i)) was studied in cultured mouse cer
ebral cortical neurones. Glu-induced responses were mediated by two me
chanisms, one independent of and the other dependent on extracellular
Ca2+, both being inhibited by TMB-8 in a dose-dependent manner. TMB-8
had no effect on [H-3]dizocilpine binding kinetics in cortical membran
e preparations. The transient and sustained phases of K+-induced incre
ases in [Ca2+](i) were also inhibited by TMB-8 in a dose-dependent man
ner. The Ca2+ channel antagonist, verapamil, blocked K+-induced respon
ses but had no effect on Glu-induced responses. Although TMB-8 display
s multiple effects, its action at voltage-gated Ca2+ channels does not
appear to contribute significantly to its inhibition of the Glu-induc
ed increase in [Ca2+](i).