The inotropic and chronotropic effects of physostigmine and neostigmine on guinea-pig isolated atria.

1 Physostigmine (0.1-1 mM) induced dose-dependent negative and neostigmine (0.1-1 mM) positive inotropic effects on driven guinea-pig isolated atria. Physostigmine decreased and neostigmine increased cardiac frequency of spontaneously beating atria. 2 The depression of amplitude of contraction by physostigmine cannot be attributed to its inhibitory effect on tissue cholinesterase. The negative inotropic action of physostigmine is not influenced by preincubation with atropine. 3 The positive inotropic effect of neostigmine is not caused by a nicotine-like action of the drug. Neostigmine (1 mM) counteracts the negative inotropic effect of acetylcholine. The possible mechanisms of action are discussed.