Local anesthetic activity of beta-adrenergic blocking drugs in the Crayfish giant axon, with reference to calcium ion.

The actions of beta-adrenergic blocking drugs, propranolol, pindolol, timolol, carteolol, sotalol and practolol, were examined regarding effects on crayfish giant axon in an attempt to determine the relationship among chemical structure and local anesthetic activity, and the interaction of these drugs with Ca++. The activities of local anesthetics such as procaine and lidocaine served for comparisons. A conventional microelectrode technique was used to obtain the resting membrane and action potentials. All drugs except sotalol and practolol dose-dependently inhibited the dV/dt and amplitude of the action potential with a slight decrease (less than 6 mV) in the resting membrane potential. The relative potencies of these drugs in the reduction of the dV/dt were as follows: propranolol 13.3, pindolol 1.7, procaine 1.0, lidocaine 0.91, timolol 0.71 and carteolol 0.22. Sotalol and practolol had little activity. The chemical structure of the drugs for local anesthetic action was closely related to that of the lipophilic aromatic group; the most potent activity seen in the naphthyl group. Potentiation of the local anesthetic activity in low Ca++ solution was obtained with pindolol, timolol, carteolol, sotalol and practolol. Reduction of the activity in high Ca++ solution was observed with propranolol, pindolol, timolol, procaine and lidocaine. These results suggest that external Ca++ competes with the local anesthetic action of the beta-adrenergic blocking drugs, at the site of the action potential generating mechanism.