Treatment of Downbeat Nystagmus in Arnold-Chiari Malformation using 3,4-Diaminopyridine

No abstract available.

Neuromuscular Blocking Actions and Mechanisms of Kanamycin, Pefloxacin and Rocuronium in the Rat Phrenic Nerve-Hemidiaphragm Preparations / 대한마취과학회지

BACKGORUND: Kanamycin (K) has been shown to block neuromuscular transmission by reducing acetylcholine release or postsynaptic action. Pefloxacin (P) may exacerbate myasthenia gravis and reduce the tau of MEPP. Rocuronium (R) is still the subject of dispute as to whether it has a selective presynaptic effect. Therefore, we undertook to compare the muscle relaxation actions and reversibilities of K, P and R. METHODS: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). Preparations were bathed in Krebs' solution ([mM]:NaCl 118, KCl 5, CaCl2 2.5, NaHCO3 30, KH2PO4 1, MgCl2 1 and glucose 11), maintained at 32degreeC and aerated with a mixture of 95% O2 and 5% CO2. isometric forces generated in response to 0.1 Hz, and 50 Hz for 1.9 seconds with supramaximal stimulation (0.2 ms, rectangular) to the phrenic nerve, were measured using a force transducer. The effects on single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % reduction. The effects on tetanic fade (TF) were calculated as % increase. K, P and R were added to the tissue bath to achieve the desired bath concentrations. EC5, EC25, EC50, EC75, and EC95 for ST, PTT and TF were calculated using a probit model. The antagonism indices of neuromuscular blockades by calcium (5 mM), 3,4-diaminopyridine (3,4-DAP) (10muM), and neostigmine (N) (250 nM) were assessed at 85+/-5% reduction (or increase). RESULTS: The potencies of ST, PTT and TF were 5.49, 5.73 and 6.30 (mM) for K, 1.90, 1.67 and 1.31 (mM) for P, and 10.81, 5.27 and 4.41 (muM) for R. The correlation between ST, PTT and TF varied for K, P and R. Neuromuscular blockades of K were reversed similarly by calcium and 3,4-DAP, and partially by N, whilst those of P were not, and ST reduction of R was reversed by 3,4-DAP (98%) and PTT and TF of R were partially reversed by 3,4-DAP and N. CONCLUSiONS: it is considered probable that K inhibits acetylcholine release and noncompetitively blocks postsynaptic sites, P postsynaptically depresses the neuromuscular transmission with acetylcholine receptor-ion channel block and that R has not only a selective presynaptic effect but also a postsynaptic block effect.

Effects of verapamil on the sustained depolarization of rat diaphragm myocyte pretreated with neostigmine or 3,4-diaminopyridine / 中国药理学与毒理学杂志

AIM　To study the effects of verapamil on end-plate potentials(EPPs) in isolated non-uniform stretched muscle preparation(INSMP) of rat diaphragms pretreated with neostigmine or 3,4-diaminopyridine(3,4-DAP). METHODS　Using conventional intracellular microelectrode recording technique. RESULTS A sustained depolarization could be induced at the end-plate area pre-incubated with 0.2－5.0 μmol·L-1 neostigmine or 1.0－4.0 mmol·L-1 3,4-DAP. In normal Tyrode solution, verapamil at a concentration of 1, 5, 10 or 20 μmol·L-1 had no significant effect on evoked endplate potentials and miniature endplate potentials. However, the sustained depolarization due to neostigmine or 3,4-DAP could be antagonized by verapamil at 5－20 μmol·L-1 and the duration of the depolarization was shortened in a concentration-dependent manner. CONCLUSIONL-type calcium ion channels can be activated by accumulated acetylcholine in the synaptic cleft and may be involved in producing sustained depolarization, while they play no role in transmitter release under normal physiological conditions.