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  • Title: Azathioprine: effects on neuromuscular transmission.
    Author: Dretchen KL, Morgenroth VH, Standaert FG, Walts LF.
    Journal: Anesthesiology; 1976 Dec; 45(6):604-9. PubMed ID: 185925.
    Abstract:
    The neuromuscular effects of azathioprine were examined in the in-vivo cat soleus muscle preparation. In concentrations ranging from 10 to 1,000 mug/kg, administered intra-arterially, the agent caused motor axons to fire repetitively and produced a dose-related increase in the force of contraction. The drug reversed neuromuscular blockage produced by d-tubocurarine and potentiated the neuromuscular blockade produced by succinylcholine. The effects of theophylline, a phosphodiesterase inhibitor, on neuromuscular transmission were identical to those produced by azathioprine. Using an in-vitro assay preparation, azathioprine was found to produce 50 per cent inhibition (IC50) of phosphodiesterase at a concentration of 2 X 10(-5) M. In the same preparation, theophylline had an IC50 of 1 X 10(-4) M. Neither agent in concentrations to 10(-2) M affected cholinesterase activity measured in vitro. It is concluded that the effects of azathioprine on neuromuscular transmission are due to inhibition of phosphodiesterase in the motor nerve terminal.
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