Summary
Local anesthetics (LA's) were examined for their ability to inhibit medullary catecholamine release from perfused cat adrenal glands in response to calcium (0.5 mM) in the presence of 56 mM KCl. LA's which are esters of p-aminobenzoic acid (including benzocaine), or which possess either an amide group (dibucaine), an amidine group (phenacaine), or an amino alkyl ether linkage (diphenhydramine) all produced a graded inhibition of the action of calcium, which was reversed by excess calcium (3 mM). Benzocaine, which does not possess an alkyl amino nitrogen, was five times more potent than procaine in depressing calciumevoked secretion; benoxinate, as well as tetracaine, which differ from procaine and its dimethyl analogue by possessing substituent groups on the aromatic ring were over thirty times more potent than procaine and dimethyl-procaine. Increasing the pH of the perfusion medium from 7.0–8.3 produced no marked alteration in the ability of procaine, tetracaine, and benzocaine to inhibit the stimulant actions of calcium. It is concluded that the aromatic ring of the LA molecule is more important than the alkyl nitrogen in determining the activity of a given agent in blocking the action of calcium.
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Supported by Research Grant AM 09237 from the National Institute of Arthritis and Metabolic Diseases, United States Public Health Service.
NATO Fellowship Awardee, 1966–1967; Permanent Address: Second Chair of Pharmacology, Naples University, Italy.
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Rubin, R.P., Miele, E. The relation between the chemical structure of local anesthetics and inhibition of calcium-evoked secretion from the adrenal medulla. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 260, 298–308 (1968). https://doi.org/10.1007/BF00537635
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DOI: https://doi.org/10.1007/BF00537635