Interaction of adrenaline with neostigmine and tubocurarine at the skeletal neuromuscular junction.

The effects of neostigmine, and of neostigmine with adrenaline, on the response of the rat isolated hemidiaphragm to stimulation of the phrenic nerve are reported. Neostigmine augmented the response: a maximum augmentation occurred at a concentration of 6.4 X 10(-7) mol litre-1. At greater concentrations of neostigmine the response was reduced. Adrenaline in the absence of neostigmine produced no significant change in the contraction response. However, in the presence of neostigmine further augmentation occurred and achieved a maximum in the presence of adrenaline 3.2 X 10(-7)-1.3 X 10(-6) mol litre-1. Adrenaline 4.0 X 10(-8)-1.3 X 10(-6) mol litre-1 combined with neostigmine 4.0 X 10(-8)-6.4 X 10(-7) mol litre-1 reversed tubocurarine-induced neuromuscular blockade more effectively than neostigmine alone (P less than 0.001). Adrenaline appeared to enhance the antagonistic effect of neostigmine by increasing acetylcholine release and by enhancing the response at the post-junctional acetylcholine receptor.