Comparative Study of the Secretory Response to Dopamine and Seven Amino Acid Conjugated Derivatives on the Blood-Perfused Canine Pancreas

Abstract

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 the drugs with Ca2+. The activities of local anesthetics, i.e., 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 [rate of voltage change] and amplitude of the action potential with a slight decrease (< 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 Ca2+ solution was obtained with pindolol, timolol, carteolol, sotalol and practolol. Reduction of the activity in high Ca2+ solution was observed with propranolol, pindolol, timolol, procaine and lidocaine. External Ca2+ competes with the local anesthetic action of the .beta.-adrenergic blocking drugs at the site of the action potential generating mechanism.