d-Tubocurarine causes neuronal death when injected directly into rat brain

d-Tubocurarine (d-TC) is a drug commonly used to produce muscle paralysis. Although it has been demonstrated to produce seizures when injected directly into the cerebral ventricles, no lasting neurotoxic effects have been reported. Data presented here suggest that amounts of d-TC as small as 1 microgram injected directly into rat hippocampus resulted in selective damage to dentate granule cells. Larger doses (5 to 10 micrograms) induced limbic and motor seizures with damage to hippocampal pyramidal cells. Other brain regions showed a differential sensitivity to direct injections. Pharmacologic studies suggest a nicotinic mechanism for both actions. The neurotoxic effects could not be elicited if d-TC was administered systemically, even when the blood-brain barrier was disrupted.