Phenacaine (UNII: V3M4D317W8) also known as holocaine is a local anesthetic used in ophthalmic medicine. Like other local anesthetics it inhibits the specific calmodulin-dependent stimulation of erythrocyte Ca2+-ATPase (ATP phosphohydrolase) and cyclic nucleotide phosphodiesterases (3',5'-cyclic-nucleotide 5'-nucleotidohydrolase) from brain and heart. Basal activities of these enzymes in the absence of calmodulin are relatively unaffected by concentrations of local anesthetics that strongly inhibit the specific stimulation by calmodulin. Increasing calmodulin, but not Ca2+, overcomes the inhibitory action of the local anesthetics on brain phosphodiesterase. However, excess calmodulin does not fully restore activity of erythrocyte CA2+-stimulated ATPase. Although the mechanism(s) by which the local anesthetics act is unclear, they inhibit binding of 125I-labeled calmodulin to the erythrocyte membrane. Antagonism of calmodulin provides a molecular mechanism that may explain the inhibition of many Ca2+-dependent cellular processes by local anesthetics--e.g., Ca2+ transport, exocytosis, excitation-contraction coupling, non-muscle-cell motility, and aggregation. Phenacaine hydrochloride is registered by FDA as an anorectal drug product and is in the list of OTC active ingredients. The Ointment Ophthalmic Holocaine and Epinephrine (1.5% phenacaine hydrochloride) were distributed by National Drug Co., a corporation, Philadelphia, Pa. and in 1939 and was alleged to be misbranded since it contained less phenacaine hydrochloride than indicated by the labeling.