PHARMACOLOGIC STUDIES WITH 7-BENZYL-1-ETHYL-1,4-DIHYDRO-4-OXO-1 ,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID

¹ Sterling-Winthrop Research Institute, Rensselaer, New York

7-Benzyl-1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-earboxylic acid (NCA) is a potent locomotor stimulant in a variety of laboratory animals. The drug was studied to determine the pertinent pharmacology and possible mechanism of action. NCA was compared with d-amphetamine and pipradrol in locomotor activity experiments in combination with reserpine and -methyl-dl-tyrosine. Additional motor activity studies involving combinations of NCA with phenoxybenzamine and p-chlorophenylalanine were also done. Reserpine blocked NCA-induced and pipradrolinduced hypermotility whereas it only reduced d-amphetamine-induced hypermotility. -Methyl-dl-tyrosine antagonized the activity of d-amphetamine but only partially blocked pipradrol and was completely ineffective vs. NCA. Phenoxybenzamine antagonized and p-chlorophenylalanine had no effect on the NCA-induced hypermotility. The mechanism of action of NCA appears to be dependent upon catecholamines and the drug may act by altering norepinephrine uptake or by releasing norepinephrine from the storage pool. These studies also suggested different mechanisms of action for d-amphetamine and pipradrol.

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