EFFECTS OF THE QUINOLINE DERIVATIVES QUININE, QUINIDINE, AND CHLOROQUINE ON NEUROMUSCULAR-TRANSMISSION

The quinoline derivatives quinine, its stereoisomer quinidine, and chl oroquine may worsen or provoke disorders of neuromuscular transmission . In this study, we investigate effects of these drugs on neuromuscula r transmission by conventional microelectrode as well as patch-clamp t echniques. At 5 x 10(-5) M, quinine, quinidine, and chloroquine reduce d the quantal content of the end-plate potential by 37-45%. Between 10 (-6) and 10(-4) M, all 3 drugs progressively decreased the amplitude a nd decay time constant of miniature end-plate potential (MEPP) and min iature end-plate current (MEPC); at 5 x 10(-3) M, the MEPP became unde tectable. The effect on the MEPP was not reversed by 1 mu g/ml neostig mine. Single-channel patch-clamp analysis of the effects of quinine sh owed that this agent causes a long-lived open-channel as well as a clo sed-channel block of AChR. Tests for competitive inhibition or desensi tization of the acetylcholine receptor (AChR) by quinine in concentrat ions that had a marked effect on the MEPC and on single-channel open a nd closed intervals were negative. Because quinoline drugs adversely a ffect both presynaptic and postsynaptic aspects of neuromuscular trans mission at concentrations close to those employed in clinical practice , they should not be used, or used with caution, in disorders that com promise the safety margin of neuromuscular transmission.