ACUTE VASCULAR TOLERANCE TO MORPHINE, ISONIPECAINE (DEMEROL), AND METHADON (AMIDONE) IN THE DOG

¹ Department of Pharmacology, School of Medicine, University of Michigan, Ann Arbor, Michigan

In the anesthetized dog intravenous administration of morphine, Demerol or Amidone results in an acute fall in blood pressure with gradual recovery occurring over a variable period of time. Repeated injection of morphine (2 or 4 mg. per kg.) results in complete vascular tolerance. Only partial acute tolerance develops to Demerol (5 mg. per kg.) administered similarly. The acute drop in blood pressure and rapid recovery, without the succeeding prolonged period of hypotension occurring after two doses of Amidone demonstrates the development of tolerance to the prolonged depressor effect of this drug.

Tolerance to morphine confers only partial tolerance to Demerol and no tolerance to the acute hypotensive effect of Amidone. Repeated injection of Demerol produces no tolerance to morphine, no tolerance to the acute fall in blood pressure produced by Amidone, but tolerance to the prolonged period of hypotension occurring after a single dose of this latter drug.

Repeated administration of Amidone results in no cross tolerance to morphine or Demerol.

Anesthesia interferes with the compensatory mechanisms involved in the development of acute tolerance.

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