MIXED ACTIONS OF TMB-8 AS A CA2-NEURONS( ANTAGONIST IN CULTURED MOUSECORTICAL)

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).