PHARMACOLOGICAL STUDIES ON TARICHATOXIN, A POTENT NEUROTOXIN

¹ Max C. Fleischmann Laboratories of the Medical Sciences, Stanford University School of Medicine, Palo Alto, California, and Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York

Tarichatoxin, a purified substance with the probable molecular formula of C₁₁H₁₇N₃O₈ can be obtained from the eggs of the California salamander, Taricha torosa. Upon parenteral administration in doses of 1.4 to 3 µg/kg to anesthetized cats, tarichatoxin caused profound hypotension and weakness of neurally elicited contractions of the nictitating membrane and skeletal muscles. The minimum lethal dose in mice was about 8 µg/kg and LD50 about 10 µg/kg, death being preceded by clonic convulsions and paralysis of skeletal and respiratory muscles. In a concentration of 5 mg/l the toxin produced corneal anesthesia of short duration in the rabbit's eye. Action potentials of the desheathed frog nerve were readily blocked by tarichatoxin. A concentration of 1 µg/l (0.003 µM) produced partial block while a concentration of 10 µg/l (0.03 µM) produced complete block. The axonal block was not preceded, accompanied, or followed by any change in the resting potential. The concentrations required to produce axonal block in vitro are in agreement with those producing systemic effects if the tarichatoxin is assumed to be homogeneously distributed in the body water. Since the cholinergic and adrenergic receptors in the autonomic ganglia and in the various effector cells are not affected by tarichatoxin, almost all the systemic effects produced by tarichatoxin can be ascribed to a block of the preganglionic cholinergic and the somatic motor nerves. Tarichatoxin is some 160,000 times more potent than cocaine in producing axonal block. Its pharmacological properties are compared with those of saxitoxin and tetrodotoxin.

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