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Fluorinated 4-quinolones are widely used antibiotics. Several case reports describe the exacerbation of muscle weakness in myasthenia gravis patients treated with fluoroquinolones. We studied the effects of norfloxacin, ofloxacin, and pefloxacin on miniature endplate potentials (MEPPs) and currents. These antibiotics progressively decreased the amplitude of the MEPPs as drug concentrations were increased from 12.5 to 100 mg/L. Fluoroquinolones should be used only with great caution in disorders that compromise the safety margin of neuromuscular transmission.

The quinoline derivatives quinine, its stereoisomer quinidine, and chloroquine may worsen or provoke disorders of neuromuscular transmission. In this study, we investigate effects of these drugs on neuromuscular transmission by conventional microelectrode as well as patch-clamp techniques. At 5 x 10(-5) M, quinine, quinidine, and chloroquine reduced 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 and decay time constant of miniature end-plate potential (MEPP) and miniature end-plate current (MEPC); at 5 x 10(-3) M, the MEPP became undetectable. The effect on the MEPP was not reversed by 1 microgram/mL neostigmine. Single-channel patch-clamp analysis of the effects of quinine showed that this agent causes a long-lived open-channel as well as a closed-channel block of AChR. Tests for competitive inhibition or desensitization of the acetylcholine receptor (AChR) by quinine in concentrations that had a marked effect on the MEPC and on single-channel open and closed intervals were negative. Because quinoline drugs adversely affect both presynaptic and postsynaptic aspects of neuromuscular transmission at concentrations close to those employed in clinical practice, they should not be used, or used with caution, in disorders that compromise the safety margin of neuromuscular transmission.

The congenital myasthenic syndrome constitute a group of genetic disorders affecting neuromuscular transmission. This group includes presynaptic as well as postsynaptic defects. In several congenital myasthenic syndromes, it was possible to characterize the underlying mechanism by applying modern in vitro electrophysiological methods, like single-channel recordings. These genetic disorders include defects of acetylcholine release, absence of the endplate-specific form of acetylcholinesterase, and kinetic abnormalities of the acetylcholine receptor. Recently several mutations of the acetylcholine receptor have been characterized. Clinical features of these syndromes, diagnostic work-up, and treatment are described in detail. These diseases present usually within the first 2 years of life, however, in some syndromes manifestation during adulthood is possible. The clinical spectrum ranges from mild muscle weakness to severe disability with lifethreatening episodes. Only some syndromes respond to acetylcholinesterase inhibitors. Further elucidation of these syndromes will not only lead to improved treatment, but should contribute to our understanding of synaptic transmission.

(-)-Ephedrine has been used in the treatment of patients with myasthenia gravis. To investigate the possible effects of ephedrine on neuromuscular transmission, canine intercostal muscle endplates were studied by microelectrode techniques. At concentrations less than 10(-4) M, ephedrine had no effect on neuromuscular transmission. At a concentration of 10(-4) M, ephedrine increased the quantal content of the endplate potential by 21%. The presynaptic store of acetylcholine quanta available for immediate release was unchanged, but the probability of quantal release was increased by 16%. At this concentration, ephedrine decreased the amplitude of the miniature endplate potential by 38%. In the presence of 10(-3) M ephedrine, the miniature endplate potentials and currents became undetectable. The kinetic properties of the acetylcholine receptor channel were studied by analysis of acetylcholine-induced endplate current noise. At 10(-4) M, ephedrine reduced the channel conductance by 43% but had no effect on the open time. At 5 x 10(-4) M, ephedrine reduced the channel conductance by 84% and increased the open time by 23 percent.