Production of Tolerance in the Rat to Octamethyl Pyrophosphoramide (OMPA).

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Abstract
When OMPA, a potent cholinesterase inhibitor, was subcut. administered to rats daily in a 0.1% aqueous soln. a tolerance was developed. For example, rats receiving 05 mg./kg. daily for 12 days subsequently tolerated for 41 days, without symptoms, a daily dose of 1 mg./kg. This latter dose killed 100% of a control group in 7 days. The tolerance was lost after a period of discontinued treatment. Blood cholinesterase levels did not continue to decrease after prolonged treatment and even tended to rise slightly during continued treatment. The possible significance of these findings in the use of OMPA in the treatment of myasthenia gravis is discussed.

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