The effects of 6-azauridine on the peripheral nervous system—II. The action on neuromuscular transmission and on striated muscle

Abstract

The effects of 6-azauridine, a cancerostatic agent, on striated muscle and on neuromuscular transmission, were studied in the isolated phrenic nerve hemidiaphragm preparation of the rat. In the directly stimulated and curarized preparation, 6-azauridine in a concentration of 2 × 10⁻⁶ to 2 × 10⁻⁴ g/ml caused a late increase in contractions. Higher concentrations (2 × 10⁻³ to 2 × 10⁻²) resulted in an initial increase in muscle contractions followed by inhibition of the contractions which developed gradually. The concentration of 6 × 10⁻² led to a decrease in muscle contractions only. In the indirectly stimulated preparation, low concentrations of the drug (2 × 10⁻⁶ to 8 × 10⁻⁵) led to a slight increase in muscle contractions. The concentration from 8 × 10⁻⁴ up to 6 × 10⁻² caused an inhibition or blockade of muscle contractions. It was possible to overcome this inhibition temporarily with physostigmine (1 × 10⁻⁵) or tetanic stimulation. The effects of 6-azauridine on the contractile mechanism of striated muscle correspond to the action on smooth muscle described previously, both being biphasic, depending on the dose. The action of 6-azauridine on neuromuscular transmission was inhibitory in the concentrations having an opposite effect on directly stimulated muscle. It is concluded that this curare-like action of 6-azauridine is non-depolarizing.