TEA also produces effects at the neuromuscular junction and at sympathetic nerve terminals. At the mechanistic level, TEA has long been known to block voltage-dependent K+ channels in nerve, and it is thought that this action is involved in the effects of TEA at sympathetic nerve terminals. With respect to activity at the neuromuscular junction, TEA has been found to be a competitive inhibitor at nicotinic acetylcholine receptors, although the details of its effect on these receptor proteins are complex. TEA also blocks Ca2+ - activated K+ channels, such as those found in skeletal muscle and pituitary cells. It has also been reported that TEA inhibits aquaporin (APQ) channels, but this still seems to be a disputed issue. A partial effect of these voltage-dependent and permeability properties within each system mentioned above is not only due to the aforementioned inhibitory properties of TEA, but also its ability to inhibit Na,K-ATPase. Acting on the extracellular vestibule of the Na,K-ATPase, inhibiting K+ access similar to ouabain, TEA further accentuates the disrupted K, and Na, gradients within each of these systems. Clinical considerations Although TEA (sometimes under the name "Etamon") was explored in a number of different clinical applications, including the treatment of hypertension, its major use seems to have been as a probe to assess the capacity for vasodilation in cases of peripheral vascular disease. Because of dangerous, even fatal reactions in some patients, as well as inconsistent cardiovascular responses, TEA was soon replaced by other drugs. TEA is not orally active. Typical symptoms produced in humans include the following: dry mouth, suppression of gastric secretion, drastic reduction of gastric motility, paralysis of urinary bladder, and relief of some forms of pain. Most studies with TEA seem to have been performed using either its chloride or bromide salt without comment as to any distinctions in effect, but Birchall and his co-workers preferred the use of TEA chloride in order to avoid the sedative effects of the bromide ion. Toxicology An extensive study of the toxicology of tetraethylammonium chloride in mice, rats and dogs was published by Gruhzit and co-workers in 1948. These workers reported the following symptoms in mice and rats receiving toxic parenteral doses: tremors, incoordination, flaccid prostration, and death from respiratory failure within 10–30 minutes; dogs exhibited similar symptoms, including incoordination, flaccid prostration, respiratory and cardiac depression, ptosis, mydriasis, erythema, and death from respiratory paralysis and circulatory collapse. After non-lethal