TACHYPHYLAXIS OF INDIRECTLY ACTING SYMPATHOMIMETIC AMINES

I DIFFERENCE OF PRESSOR EFFECT PRODUCED BY REPEATED ADMINISTRATION OF EPHEDRINE, METHAMPHETAMINE AND PHENIPRAZINE IN DOGS

Abstract

The difference in the appearance of tachyphylaxis in morphine and pentobarbital-anesthetized atropinized dog with repeated administration of three ephedrine-like drugs was studied by assessing the change of blood pressure reaction. 1) Tendency to induce tachyphylaxis was most intense in methamphetamine, followed by ephedrine. The tendency to cause tachyphylaxis of pheniprazine, which is an intense monoamine oxidase inhibitor, was milder than in other drugs. 2) Ephedrine-like drugs causes crossed tachyphylaxis with each other. Especially, when repeated administration of one of ephedrine-like drugs resulted in considerable attenuation of the degree of pressor effect or a fall of pressure (reversal effect), immediate administration of other drugs caused only a fall of blood pressure in many circumstances. 3) After administration of ephedrine-like drugs, the pressor effect due to catecholamines was potentiated. After tachyphylaxis especially the reversal effect with ephedrine-like drugs, the pressor effect to catecholamines may be somewhat attenuated but a sufficient rise was still noted. These results would indicate that the tendency to cause tachyphylaxis is related to the dosage of these drugs and their binding abllty to norepinephrine storage site in tissue.