BLOCKING OF NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTORS WITH D-SPARTEINE DERIVATIVES

The effects of d-sparteine (d-SP) and its two derivatives, N-methylsparteine (IEM-1820) and N-phenylsparteine (IEM-1821), on nicotinic acetylcholine receptors (nAChR) of the rat superior cervical ganglion neurons were studied. Membrane currents evoked by iontophoretically applied acetylcholine were recorded using the patch-clamp recording technique in the whole-cell configuration. All three compounds were found to block nAChR competitively, the blocking activity being increased with an increase in the size of the blocking molecule. The EC(50) values for d-SP, IEM-1820, and IEM-1821 were equal to 2.06 +/- 0.38 mu M (n = 3), 1.64 +/- 0.41 mu M (n = 4), and 0.65 +/- 0.17 mu M (n = 3), respectively. It was assumed that the increase in efficiency of blocking is related to the decrease in the rate of dissociation of the blocker and receptor molecules.