The Effects of Cimetidine and Famotidine on Neuromuscular Transmission and Their Interaction with Gentamicin

In the present paper, rat phrenic nerve-diaphragm preparations were used to evaluate the neuromuscular blocking activity of gentamicin, an aminoglycoside antibiotic, and of its combinations with histamine 112-recepwr blocking agents, cimetidine and famoti-dine. Gentamicin and famotidine caused partial neuro-muscular blockade when they were used alone, but cimetidine had no effect. There was no interactions between giyen histamine H2-receptor blocking drugs and reduced concentration of gentamicin (10-4M) which does not exert any neuromuscular blockade. However, when the ineffective doses of cimetidine or famotidine are added in the medium, partial inhibi-tion caused by 10-2 M gentamicin attained to complete blockade. This effect can be reversed with the addition of calcium chloride. These results Show that, if the partial blockade is present, histamine H2-receptor blocking agents can greatly compromise the neuromuscular transmission.