1. The lamotrigine analogue 619C89, utilised to reduce postischaemic and posttraumatic neuronal injury, has been shown to inhibit sodium channels and cloned N-type calcium channels. To verify whether this neuroprotective agent also blocked native calcium channels, we have tested its action in cortical pyramidal neurones, acutely isolated from the adult rat brain. 2. 619C89 inhibited more than 90% of the high voltage-activated calcium currents recorded in the whole-cell configuration. The response was relatively slow in onset (30-60 s), recovered incompletely (96%), but showed no consistent desensitization. 3. This inhibitory effect was not selective for any calcium channel subtype, being largely unaffected by omega-conotoxin-GVIA, omega-agatoxin-IVA, omega-conotoxin-MVIIC and dihydropyridine antagonists. 4. Saturating responses to 619C89 were detected for concentrations > or = 50 microM. Dose-response curves revealed that 619C89 have an approximately 8 microM binding site. 5. The effect of 619C89 was dependent on the divalent concentrations in that its potency was reduced on increase of the charge carrier up to 20 mM barium. Since the lamotrigine analogue shifted to the right the dose-dependence of the cadmium block, the 619C89-mediated inhibition of calcium currents seemed to rely on a direct interaction with the channel pore. Functional implications are discussed.